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  1. Fulltext Whole genome sequence analysis showing unique SARS-CoV-2 lineages of B.1.524 and AU.2 in Malaysia
    Zainulabid UA, Mat Yassim AS, Hussain M, Aslam A, Soffian SN, Mohd Ibrahim MS, et al.
    PLoS One, 2022;17(2):e0263678.
    PMID: 35213571 DOI: 10.1371/journal.pone.0263678
    SARS-CoV-2 has spread throughout the world since its discovery in China, and Malaysia is no exception. WGS has been a crucial approach in studying the evolution and genetic diversity of SARS-CoV-2 in the ongoing pandemic. Despite considerable number of SARS-CoV-2 genome sequences have been submitted to GISAID and NCBI databases, there is still scarcity of data from Malaysia. This study aims to report new Malaysian lineages of the virus, responsible for the sustained spikes in COVID-19 cases during the third wave of the pandemic. Patients with nasopharyngeal and/or oropharyngeal swabs confirmed COVID-19 positive by real-time RT-PCR with CT value < 25 were chosen for WGS. The selected SARS-CoV-2 isolates were then sequenced, characterized and analyzed along with 986 sequences of the dominant lineages of D614G variants currently circulating throughout Malaysia. The prevalence of clade GH and G formed strong ground for the presence of two Malaysian lineages of AU.2 and B.1.524 that has caused sustained spikes of cases in the country. Statistical analysis on the association of gender and age group with Malaysian lineages revealed a significant association (p <0.05). Phylogenetic analysis revealed dispersion of 41 lineages, of these, 22 lineages are still active. Mutational analysis showed presence of unique G1223C missense mutation in transmembrane domain of the spike protein. For better understanding of the SARS-CoV-2 evolution in Malaysia especially with reference to the reported lineages, large scale studies based on WGS are warranted.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics
  2. Fulltext Understanding the role of ACE-2 receptor in pathogenesis of COVID-19 disease: a potential approach for therapeutic intervention
    Shirbhate E, Pandey J, Patel VK, Kamal M, Jawaid T, Gorain B, et al.
    Pharmacol Rep, 2021 Dec;73(6):1539-1550.
    PMID: 34176080 DOI: 10.1007/s43440-021-00303-6
    Angiotensin-converting enzyme (ACE) and its homologue, ACE2, are commonly allied with hypertension, renin-angiotensin-aldosterone system pathway, and other cardiovascular system disorders. The recent pandemic of COVID-19 has attracted the attention of numerous researchers on ACE2 receptors, where the causative viral particle, SARS-CoV-2, is established to exploit these receptors for permitting their entry into the human cells. Therefore, studies on the molecular origin and pathophysiology of the cell response in correlation to the role of ACE2 receptors to these viruses are bringing novel theories. The varying level of manifestation and importance of ACE proteins, underlying irregularities and disorders, intake of specific medications, and persistence of assured genomic variants at the ACE genes are potential questions raising nowadays while observing the marked alteration in response to the SARS-CoV-2-infected patients. Therefore, the present review has focused on several raised opinions associated with the role of the ACE2 receptor and its impact on COVID-19 pathogenesis.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/metabolism
  3. Fulltext Structural Evaluation of the Spike Glycoprotein Variants on SARS-CoV-2 Transmission and Immune Evasion
    Salleh MZ, Derrick JP, Deris ZZ
    Int J Mol Sci, 2021 Jul 10;22(14).
    PMID: 34299045 DOI: 10.3390/ijms22147425
    The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents significant social, economic and political challenges worldwide. SARS-CoV-2 has caused over 3.5 million deaths since late 2019. Mutations in the spike (S) glycoprotein are of particular concern because it harbours the domain which recognises the angiotensin-converting enzyme 2 (ACE2) receptor and is the target for neutralising antibodies. Mutations in the S protein may induce alterations in the surface spike structures, changing the conformational B-cell epitopes and leading to a potential reduction in vaccine efficacy. Here, we summarise how the more important variants of SARS-CoV-2, which include cluster 5, lineages B.1.1.7 (Alpha variant), B.1.351 (Beta), P.1 (B.1.1.28/Gamma), B.1.427/B.1.429 (Epsilon), B.1.526 (Iota) and B.1.617.2 (Delta) confer mutations in their respective spike proteins which enhance viral fitness by improving binding affinity to the ACE2 receptor and lead to an increase in infectivity and transmission. We further discuss how these spike protein mutations provide resistance against immune responses, either acquired naturally or induced by vaccination. This information will be valuable in guiding the development of vaccines and other therapeutics for protection against the ongoing coronavirus disease 2019 (COVID-19) pandemic.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics; Spike Glycoprotein, Coronavirus/immunology; Spike Glycoprotein, Coronavirus/metabolism; Spike Glycoprotein, Coronavirus/chemistry*
  4. Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial
    Gatechompol S, Kittanamongkolchai W, Ketloy C, Prompetchara E, Thitithanyanont A, Jongkaewwattana A, et al.
    Nat Microbiol, 2022 Dec;7(12):1987-1995.
    PMID: 36376393 DOI: 10.1038/s41564-022-01271-0
    Effective mRNA SARS-CoV-2 vaccines are available but need to be stored in freezers, limiting their use to countries that have appropriate storage capacity. ChulaCov19 is a prefusion non-stabilized SARS-CoV-2 spike-protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine that we report to be stable when stored at 2-8 °C for up to 3 months. Here we report safety and immunogenicity data from a phase I open-label, dose escalation, first-in-human trial of the ChulaCov19 vaccine (NCT04566276). Seventy-two eligible volunteers, 36 of whom were aged 18-55 (adults) and 36 aged 56-75 (elderly), were enroled. Two doses of vaccine were administered 21 d apart at 10, 25 or 50 μg per dose (12 per group). The primary outcome was safety and the secondary outcome was immunogenicity. All three dosages of ChulaCov19 were well tolerated and elicited robust dose-dependent and age-dependent B- and T-cell responses. Transient mild/moderate injection site pain, fever, chills, fatigue and headache were more common after the second dose. Four weeks after the second dose, in the adult cohort, MicroVNT-50 geometric mean titre against wild-type SARS-CoV-2 was 848 (95% CI, 483-1,489), 736 (459-1,183) and 1,140 (854-1,522) IU ml-1 at 10, 25 and 50 μg doses, respectively, versus 285 (196-413) IU ml-1 for human convalescent sera. All dose levels elicited 100% seroconversion, with geometric mean titre ratios 4-8-fold higher than for human convalescent sera (P spike protein is safe and highly immunogenic.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics
  5. Fulltext SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals
    Lam SD, Bordin N, Waman VP, Scholes HM, Ashford P, Sen N, et al.
    Sci Rep, 2020 Oct 05;10(1):16471.
    PMID: 33020502 DOI: 10.1038/s41598-020-71936-5
    SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/metabolism; Spike Glycoprotein, Coronavirus/chemistry*
  6. SARS-CoV-2 seroprevalence and antibody trends in vaccinated, multi-ethnic healthcare employees
    Beh CC, Zulkufli NS, Loh LM, Cheng KW, Choo LM, Cheah MW, et al.
    Trop Biomed, 2021 Dec 01;38(4):552-560.
    PMID: 35001921 DOI: 10.47665/tb.38.4.098
    Understanding of antibody kinetics against SARS-CoV-2 and its vaccines is rapidly evolving. This study aims to (1) determine post-vaccination seroprevalence; (2) compare antibody levels between vaccine types and various clinical/demographic determinants; and (3) determine post-vaccination antibody concentrations against time. This is a retrospective cross-sectional study involving 148 healthcare employees all over Malaysia. IgG Spike (RBD), IgM Spike and IgG Nucleocapsid concentration medians were compared using Mann-Whitney U or Kruskal-Wallis tests. Chi Square and Spearman correlation coefficient tests were performed to identify variables associated with antibody titers. A scatter plot of IgG Spike (RBD) against time from last vaccine dose was also plotted. At 1-month post-vaccination, all employees successfully seroconverted regardless of vaccine type, health status and COVID- 19 history. Comirnaty, convalescent, female or Malay vaccinees had significantly higher IgG Spike (RBD) titers compared to their respective counterparts. No correlation was found between age and IgG Spike (RBD) levels. Concentration of all three antibodies waned with time post-vaccination, with IgM Spike and IgG Nucleocapsid waning faster than IgG Spike (RBD).
    Matched MeSH terms: Spike Glycoprotein, Coronavirus
  7. Fulltext Protective Immunity against SARS Subunit Vaccine Candidates Based on Spike Protein: Lessons for Coronavirus Vaccine Development
    Khalaj-Hedayati A
    J Immunol Res, 2020;2020:7201752.
    PMID: 32695833 DOI: 10.1155/2020/7201752
    The recent outbreak of the novel coronavirus disease, COVID-19, has highlighted the threat that highly pathogenic coronaviruses have on global health security and the imminent need to design an effective vaccine for prevention purposes. Although several attempts have been made to develop vaccines against human coronavirus infections since the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003, there is no available licensed vaccine yet. A better understanding of previous coronavirus vaccine studies may help to design a vaccine for the newly emerged virus, SARS-CoV-2, that may also cover other pathogenic coronaviruses as a potentially universal vaccine. In general, coronavirus spike protein is the major antigen for the vaccine design as it can induce neutralizing antibodies and protective immunity. By considering the high genetic similarity between SARS-CoV and SARS-CoV-2, here, protective immunity against SARS-CoV spike subunit vaccine candidates in animal models has been reviewed to gain advances that can facilitate coronavirus vaccine development in the near future.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics; Spike Glycoprotein, Coronavirus/immunology*
  8. Properties of Coronavirus and SARS-CoV-2
    Malik YA
    Malays J Pathol, 2020 Apr;42(1):3-11.
    PMID: 32342926
    were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (α,β,γ,δ), human coronaviruses (HCoVs) are classified under α-CoV (HCoV-229E and NL63) and β-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a β-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics
  9. Fulltext Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak
    Zhang T, Wu Q, Zhang Z
    Curr Biol, 2020 04 06;30(7):1346-1351.e2.
    PMID: 32197085 DOI: 10.1016/j.cub.2020.03.022
    An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in the city of Wuhan in China and has widely spread worldwide. Currently, it is vital to explore potential intermediate hosts of SARS-CoV-2 to control COVID-19 spread. Therefore, we reinvestigated published data from pangolin lung samples from which SARS-CoV-like CoVs were detected by Liu et al. [1]. We found genomic and evolutionary evidence of the occurrence of a SARS-CoV-2-like CoV (named Pangolin-CoV) in dead Malayan pangolins. Pangolin-CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the whole-genome level. Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Five key amino acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and SARS-CoV-2, but four amino acid mutations are present in RaTG13. Both Pangolin-CoV and RaTG13 lost the putative furin recognition sequence motif at S1/S2 cleavage site that can be observed in the SARS-CoV-2. Conclusively, this study suggests that pangolin species are a natural reservoir of SARS-CoV-2-like CoVs.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/chemistry
  10. Phylogenomic analysis of SARS-CoV-2 from third wave clusters in Malaysia reveals dominant local lineage B.1.524 and persistent spike mutation A701V
    Suppiah J, Kamel KA, Mohd-Zawawi Z, Afizan MA, Yahya H, Md-Hanif SA, et al.
    Trop Biomed, 2021 Sep 01;38(3):289-293.
    PMID: 34362872 DOI: 10.47665/tb.38.3.070
    The emergence of a third wave of COVID-19 infection in Malaysia since September 2020 has led to imminent changes in public health prevention and control measures. As high as 96.2% of registered COVID-19 cases and 88.5% of confirmed deaths in Malaysia occurred during this third wave of infection. A phylogenomic study on 258 SARS-CoV-2 full genomes from February 2020-February 2021 has led to the discovery of a novel Malaysian lineage B.1.524. This lineage contains another spike mutation A701V that co-exists with the D614G spike mutation that was predominant in most of the third-wave clusters. The study provides vital genomic insights on the rapid spread of the SARS-CoV-2 variants in Malaysia in conjunction with the presence of a dominant SARS-CoV-2 lineage during the third wave of COVID-19 infection.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics*
  11. Fulltext Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) of SARS-CoV-2 spike infectivity and pathogenicity: A comparative sequence and structural-based computational assessment
    Kumar S, Karuppanan K, Subramaniam G
    J Med Virol, 2022 Oct;94(10):4780-4791.
    PMID: 35680610 DOI: 10.1002/jmv.27927
    The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron's receptor-binding domain (RBD) and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterizing in the RBD, we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and negative electrostatic surface potential human angiotensin-converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild-type (WT). Negative electrostatic potential of N-terminal domain (NTD) of the spike protein value indicates that the Omicron variant binds receptors less efficiently than the WT. Given that at least one receptor is highly expressed in lung and bronchial cells, the electrostatic potential of NTD negative value could be one of the factors contributing to why the Omicron variant is thought to be less harmful to the lower respiratory tract. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, and R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics
  12. Fulltext N-terminal domain of SARS CoV-2 spike protein mutation associated reduction in effectivity of neutralizing antibody with vaccinated individuals
    Singh Y, Fuloria NK, Fuloria S, Subramaniyan V, Meenakshi DU, Chakravarthi S, et al.
    J Med Virol, 2021 Oct;93(10):5726-5728.
    PMID: 34232521 DOI: 10.1002/jmv.27181
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics*; Spike Glycoprotein, Coronavirus/immunology
  13. Multi-Targeted Molecular Docking and Drug-Likeness Evaluation of some Nitrogen Heterocyclic Compounds Targeting Proteins Involved in the Development of COVID-19
    Hui LY, Mun CS, Sing LC, Rajak H, Karunakaran R, Ravichandran V
    Med Chem, 2023;19(3):297-309.
    PMID: 35713125 DOI: 10.2174/1573406418666220616110351
    BACKGROUND: The severe acute respiratory syndrome coronavirus-2 is causing a disaster through coronavirus disease-19 (COVID-19), affecting the world population with a high mortality rate. Although numerous scientific efforts have been made, we do not have any specific drug for COVID-19 treatment.

    OBJECTIVE: Aim of the present study was to analyse the molecular interaction of nitrogen heterocyclic based drugs (hydroxychloroquine, remdesivir and lomefloxacin) with various SARSCoV- 2 proteins (RdRp, PLPro, Mpro and spike proteins) using a molecular docking approach.

    METHODS: We have performed docking study using PyRx software, and Discovery Studio Visualizer was used to visualise the molecular interactions. The designed nitrogen heterocyclic analogues were checked for Lipinski's rule of five, Veber's Law and Adsorption, Distribution, Metabolism, and Excretion (ADME) threshold. After obtaining the docking results of existing nitrogen heterocyclic drugs, we modified the selected drugs to get molecules with better affinity against SARS-CoV-2.

    RESULTS: Hydroxychloroquine bound to RdRp, spike protein, PLPro and Mpro at -5.2, -5.1, -6.7 and -6.0 kcal/mol, while remdesivir bound to RdRp, spike protein, PLPro, and Mpro at -6.1, -6.9, -6.4 and -6.9 kcal/mol, respectively. Lomefloxacin bound to RdRp, spike protein, PLPro and Pro at -6.4, -6.6, -7.2 and -6.9 kcal/mol. ADME studies of all these compounds indicated lipophilicity and high gastro intestine absorbability. The modified drug structures possess better binding efficacy towards at least one target than their parent compounds.

    CONCLUSION: The outcome reveals that the designed nitrogen heterocyclics could contribute to developing the potent inhibitory drug SARS-CoV-2 with strong multi-targeted inhibition ability and reactivity.

    Matched MeSH terms: Spike Glycoprotein, Coronavirus
  14. Fulltext Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19
    Daood U, Gopinath D, Pichika MR, Mak KK, Seow LL
    Molecules, 2021 Apr 12;26(8).
    PMID: 33921378 DOI: 10.3390/molecules26082214
    To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38-7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein's binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/metabolism*; Spike Glycoprotein, Coronavirus/chemistry
  15. Fulltext Microarray Profiling of Vaccination-Induced Antibody Responses to SARS-CoV-2 Variants of Interest and Concern
    Svetlova J, Gustin D, Manuvera V, Shirokov D, Shokina V, Prusakov K, et al.
    Int J Mol Sci, 2022 Oct 30;23(21).
    PMID: 36362010 DOI: 10.3390/ijms232113220
    Mutations in surface proteins enable emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to escape a substantial fraction of neutralizing antibodies and may thus weaken vaccine-driven immunity. To compare available vaccines and justify revaccination, rapid evaluation of antibody (Ab) responses to currently circulating SARS-CoV-2 variants of interest (VOI) and concern (VOC) is needed. Here, we developed a multiplex protein microarray-based system for rapid profiling of anti-SARS-CoV-2 Ab levels in human sera. The microarray system was validated using sera samples from SARS-CoV-2-free donors and those diagnosed with COVID-19 based on PCR and enzyme immunoassays. Microarray-based profiling of vaccinated donors revealed a substantial difference in anti-VOC Ab levels elicited by the replication-deficient adenovirus vector-base (Sputnik V) and whole-virion (CoviVac Russia COVID-19) vaccines. Whole-virion vaccine-induced Abs showed minor but statistically significant cross-reactivity with the human blood coagulation factor 1 (fibrinogen) and thrombin. However, their effects on blood clotting were negligible, according to thrombin time tests, providing evidence against the concept of pronounced cross-reactivity-related side effects of the vaccine. Importantly, all samples were collected in the pre-Omicron period but showed noticeable responses to the receptor-binding domain (RBD) of the Omicron spike protein. Thus, using the new express Ab-profiling system, we confirmed the inter-variant cross-reactivity of the anti-SARS-CoV-2 Abs and demonstrated the relative potency of the vaccines against new VOCs.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics
  16. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins
    Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou JJ, et al.
    Nature, 2020 07;583(7815):286-289.
    PMID: 32380510 DOI: 10.1038/s41586-020-2313-x
    The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics
  17. Fulltext Isolation and molecular characterization of type I and type II feline coronavirus in Malaysia
    Amer A, Siti Suri A, Abdul Rahman O, Mohd HB, Faruku B, Saeed S, et al.
    Virol J, 2012 Nov 21;9:278.
    PMID: 23171743 DOI: 10.1186/1743-422X-9-278
    BACKGROUND: Feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV) are two important coronaviruses of domestic cat worldwide. Although FCoV is prevalent among cats; the fastidious nature of type I FCoV to grow on cell culture has limited further studies on tissue tropism and pathogenesis of FCoV. While several studies reported serological evidence for FCoV in Malaysia, neither the circulating FCoV isolated nor its biotypes determined. This study for the first time, describes the isolation and biotypes determination of type I and type II FCoV from naturally infected cats in Malaysia.

    FINDINGS: Of the total number of cats sampled, 95% (40/42) were RT-PCR positive for FCoV. Inoculation of clinical samples into Crandell feline kidney cells (CrFK), and Feline catus whole fetus-4 cells (Fcwf-4), show cytopathic effect (CPE) characterized by syncytial cells formation and later cell detachment. Differentiation of FCoV biotypes using RT-PCR assay revealed that, 97.5% and 2.5% of local isolates were type I and type II FCoV, respectively. These isolates had high sequence homology and phylogenetic similarity with several FCoV isolates from Europe, South East Asia and USA.

    CONCLUSIONS: This study reported the successful isolation of local type I and type II FCoV evident with formation of cytopathic effects in two types of cell cultures namely the CrFK and Fcwf-4 , where the later cells being more permissive. However, the RT-PCR assay is more sensitive in detecting the antigen in suspected samples as compared to virus isolation in cell culture. The present study indicated that type I FCoV is more prevalent among cats in Malaysia.

    Matched MeSH terms: Spike Glycoprotein, Coronavirus
  18. In silico screening of Allium cepa phytochemicals for their binding abilities to SARS and SARS-CoV-2 3C-like protease and COVID-19 human receptor ACE-2
    Bondhon TA, Fatima A, Jannat K, Hasan A, Jahan R, Nissapatorn V, et al.
    Trop Biomed, 2021 Jun 01;38(2):214-221.
    PMID: 34172713 DOI: 10.47665/tb.38.2.060
    Corona virus SARS-CoV-2-induced viral disease (COVID-19) is a zoonotic disease that was initially transmitted from animals to humans. The virus surfaced towards the end of December 2019 in Wuhan, China where earlier SARS (Severe Acute Respiratory Syndrome) had also surfaced in 2003. Unlike SARS, SARS-CoV-2 (a close relative of the SARS virus) created a pandemic, and as of February 24 2021, caused 112,778,672 infections and 2,499,252 deaths world-wide. Despite the best efforts of scientists, no drugs against COVID-19 are yet in sight; five vaccines have received emergency approval in various countries, but it would be a difficult task to vaccinate twice the world population of 8 billion. The objective of the present study was to evaluate through in silico screening a number of phytochemicals in Allium cepa (onion) regarding their ability to bind to the main protease of COVID-19 known as the 3C-like protease or 3CLpro, (PDB ID: 6LU7), 3CLpro of SARS (PDB ID: 3M3V), and human angiotensin converting enzyme-2 (ACE-2), [PDB ID: 1R42], which functions as a receptor for entry of the virus into humans. Molecular docking (blind docking, that is docking not only against any target pocket) were done with the help of AutoDockVina. It was observed that of the twenty-two phytochemicals screened, twelve showed good binding affinities to the main protease of SARS-CoV-2. Surprisingly, the compounds also demonstrated good binding affinities to ACE-2. It is therefore very likely that the binding affinities shown by these compounds against both 3CLpro and ACE-2 merit further study for their potential use as therapeutic agents.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/metabolism
  19. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins
    Lam TT, Jia N, Zhang YW, Shum MH, Jiang JF, Zhu HC, et al.
    Nature, 2020 07;583(7815):282-285.
    PMID: 32218527 DOI: 10.1038/s41586-020-2169-0
    The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics; Spike Glycoprotein, Coronavirus/chemistry
  20. Fulltext Haplotype distribution of SARS-CoV-2 variants in low and high vaccination rate countries during ongoing global COVID-19 pandemic in early 2021
    Bui NN, Lin YT, Huang SH, Lin CW
    Infect Genet Evol, 2022 01;97:105164.
    PMID: 34848355 DOI: 10.1016/j.meegid.2021.105164
    The widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuously impacts our economic and public health. The potential of emerging variants to increase transmissibility and evade vaccine-induced immunity lets us put more effort to research on viral mutations and explore the pathogenic haplotypes. In this study, we characterized the haplotype and sub-haplotype diversity of SARS-CoV-2 global variants in January-March and the areas with low and high COVID19 vaccination rates in May 2021 by analyzing viral proteome of complete genome sequences published. Phylogenetic tree analysis of the proteomes of SARS-CoV-2 variants with Neighbor-Joining and Maximum Parsimony methods indicated that haplotype 2 variant with nsp12 P323L and Spike D614G was dominant (98.81%), including new sub-haplotypes 2A_1 to 2A_3, 2B_1 to 2B_3, and 2C_1 to 2C_2 emerged post-one-year COVID-19 outbreak. In addition, the profiling of sub-haplotypes indicated that sub-haplotype 2A_1 with the mutations at N501Y, A570D, D614G, P681H, T716I, S982A, and D118H in Spike was over 58% in May 2021 in the high partly vaccinated rate group (US, Canada, and Germany). Meanwhile, the new haplotype 2C_3 bearing the mutations at EFR156-158del, T19R, A222V, L452R, T478K, and D614G in Spike occupied over 54.8% in May 2021 in the low partly vaccinated rate group (India, Malaysia, Taiwan, and Vietnam). Sub-haplotypes 2A_1 and 2C_3 had a meaningful alternation of ACE2-specific recognition site, neutralization epitopes, and furin cleavage site in SARS-CoV-2 Spike protein. The results discovered the haplotype diversity and new sub-haplotypes of SARS-CoV-2 variants post one-year pandemic in January-March 2021, showing the profiles of sub-haplotypes in the groups with low and high partly vaccinated rates in May 2021. The study reports the emergence of new SARS-CoV-2 sub-haplotypes during ongoing pandemic and vaccination in early 2021, which might help inform the response to vaccination strategies.
    Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics*; Spike Glycoprotein, Coronavirus/metabolism
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