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Omicron and Delta variant of SARS-CoV-2: A comparative computational study of spike protein

Kumar S, Thambiraja TS, Karuppanan K, Subramaniam G

J Med Virol, 2022 Apr;94(4):1641-1649.
PMID: 34914115 DOI: 10.1002/jmv.27526

Emerging severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, especially those of concern, may have an impact on the virus's transmissibility and pathogenicity, as well as diagnostic equipment performance and vaccine effectiveness. Even though the SARS-CoV-2 Delta variant (B.1.617.2) emerged during India's second wave of infections, Delta variants have grown dominant internationally and are still evolving. On November 26, 2021, World Health Organization identified the variant B.1.1.529 as a variant of concern, naming it Omicron, based on evidence that Omicron contains numerous mutations that may influence its behavior. However, the mode of transmission and severity of the Omicron variant remains unknown. We used computational studies to examine the Delta and Omicron variants in this study and found that the Omicron variant had a higher affinity for human angiotensin-converting enzyme 2 (ACE2) than the Delta variant due to a significant number of mutations in the SARS-CoV-2 receptor-binding domain (RBD), indicating a higher potential for transmission. Based on docking studies, the Q493R, N501Y, S371L, S373P, S375F, Q498R, and T478K mutations contribute significantly to high binding affinity with human ACE2. In comparison to the Delta variant, both the entire spike protein and the RBD in Omicron include a high proportion of hydrophobic amino acids such as leucine and phenylalanine. These amino acids are located within the protein's core and are required for structural stability. We observed a disorder-order transition in the Omicron variant between spike protein RBD regions 468-473, and it may be significant in the influence of disordered residues/regions on spike protein stability and binding to ACE2. A future study might investigate the epidemiological and biological consequences of the Omicron variant.

Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics; Spike Glycoprotein, Coronavirus/chemistry*
Fulltext Carnosine to Combat Novel Coronavirus (nCoV): Molecular Docking and Modeling to Cocrystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein

Saadah LM, Deiab GIA, Al-Balas Q, Basheti IA

Molecules, 2020 Nov 28;25(23).
PMID: 33260592 DOI: 10.3390/molecules25235605

AIMS: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. The current paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 cocrystallized with nCoV spike protein.
METHODS: First, the starting point was ACE2 inhibitors and their structure-activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. Parallel, at all stages, the authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 with nCoV spike protein.
RESULTS: Carnosine emerged as the best-known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the protein-protein structure, carnosine bound with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49.
CONCLUSION: Carnosine has promising inhibitory interactions with host ACE2 and nCoV spike protein and hence could offer a potential mitigating effect against the current COVID-19 pandemic.

Matched MeSH terms: Spike Glycoprotein, Coronavirus/metabolism; Spike Glycoprotein, Coronavirus/chemistry
Fulltext Arthropod Ectoparasites Have Potential to Bind SARS-CoV-2 via ACE

Lam SD, Ashford P, Díaz-Sánchez S, Villar M, Gortázar C, de la Fuente J, et al.

Viruses, 2021 04 19;13(4).
PMID: 33921873 DOI: 10.3390/v13040708

Coronavirus-like organisms have been previously identified in Arthropod ectoparasites (such as ticks and unfed cat flea). Yet, the question regarding the possible role of these arthropods as SARS-CoV-2 passive/biological transmission vectors is still poorly explored. In this study, we performed in silico structural and binding energy calculations to assess the risks associated with possible ectoparasite transmission. We found sufficient similarity between ectoparasite ACE and human ACE2 protein sequences to build good quality 3D-models of the SARS-CoV-2 Spike:ACE complex to assess the impacts of ectoparasite mutations on complex stability. For several species (e.g., water flea, deer tick, body louse), our analyses showed no significant destabilisation of the SARS-CoV-2 Spike:ACE complex, suggesting these species would bind the viral Spike protein. Our structural analyses also provide structural rationale for interactions between the viral Spike and the ectoparasite ACE proteins. Although we do not have experimental evidence of infection in these ectoparasites, the predicted stability of the complex suggests this is possible, raising concerns of a possible role in passive transmission of the virus to their human hosts.

Matched MeSH terms: Spike Glycoprotein, Coronavirus/genetics; Spike Glycoprotein, Coronavirus/metabolism; Spike Glycoprotein, Coronavirus/chemistry
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
Fulltext Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak

Zhang T, Wu Q, Zhang Z

Curr Biol, 2020 Apr 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
Fulltext Immunogenicity, reactogenicity, and safety of a second booster with BNT162b2 or full-dose mRNA-1273: A randomized VACCELERATE trial in adults aged ≥75 years (EU-COVAT-1-AGED Part B)

Stemler J, Yeghiazaryan L, Stephan C, Mohn KG, Carcas-Sansuan AJ, Rodriguez ER, et al.

Int J Infect Dis, 2024 Sep;146:107161.
PMID: 38992789 DOI: 10.1016/j.ijid.2024.107161

OBJECTIVES: To assess the safety and immunogenicity of a fourth vaccination (second booster) in individuals aged ≥75 years.
METHODS: Participants were randomized to BNT162b2 (Comirnaty, 30 µg) or messenger RNA (mRNA)-1273 (Spikevax, 100 µg). The primary end point was the rate of two-fold antibody titer increase 14 days after vaccination, targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. The secondary end points included changes in neutralizing activity against wild-type and 25 variants. Safety was assessed by monitoring solicited adverse events (AEs) for 7 days.
RESULTS: A total of 269 participants (mean age 81 years, mRNA-1273 n = 135/BNT162b2 n = 134) were included. Two-fold anti-RBD immunoglobulin (Ig) G titer increase was achieved by 101 of 129 (78%) and 116 of 133 (87%) subjects in the BNT162b2 and the mRNA-1273 group, respectively (P = 0.054). A second booster of mRNA-1273 provided higher anti-RBD IgG geometric mean titer: 21.326 IU/mL (95% confidence interval: 18.235-24.940) vs BNT162b2: 15.181 IU/mL (95% confidence interval: 13.172-17.497). A higher neutralizing activity was noted for the mRNA-1273 group. The most frequent AE was pain at the injection site (51% in mRNA-1273 and 48% in BNT162b2). Participants in the mRNA-1273 group had less vaccine-related AEs (30% vs 39%).
CONCLUSIONS: A second booster of either BNT162b2 or mRNA-1273 provided substantial IgG increase. Full-dose mRNA-1273 provided higher IgG levels and neutralizing capacity against SARS-CoV-2, with similar safety profile for subjects of advanced age.

Matched MeSH terms: Spike Glycoprotein, Coronavirus/immunology
Immunoinformatics-guided design of a conserved multi-epitope vaccine candidate against pathogenic human coronaviruses

Lim CP, Bingöl EN, Oliveira JIN, Chuah C, Khan MA, Douradinha B, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2026 Oct;399(13):21391-21409.
PMID: 42484859 DOI: 10.1007/s00210-026-05714-x

Despite the global decline in COVID-19 incidence, the continued emergence of immune-evasive SARS-CoV-2 variants underscores the urgent need for next-generation vaccines capable of providing broad protection. To characterise and design a broad-spectrum recombinant multiepitope vaccine candidate against pathogenic human coronaviruses using an immunoinformatics approach. Conserved antigenic regions within the spike (S), nucleocapsid (N) and membrane (M) proteins were identified from multiple SARS-CoV-2 variants through multiple sequence alignment. High-affinity T-cell and B-cell epitopes were screened and assembled into recombinant vaccine construct (RVC). The RVC was evaluated for antigenicity, allergenicity, toxicity and physicochemical properties, followed by tertiary structure prediction and validation. Molecular docking with Toll-like receptor 3 (TLR-3) and molecular dynamics (MD) simulations with MM-GBSA binding free energy calculations were performed, alongside in silico immune simulation. The RVC comprised four HLA class I-restricted epitopes, 27 HLA class II-restricted epitopes and five linear B-cell epitopes, with predicted global population coverage of 99.99%. The construct demonstrated high antigenicity, non-allergenicity and favourable physicochemical stability. Molecular docking showed stable interaction with TLR-3, supported by MD simulations and a favourable MM-GBSA binding free energy of - 5.19 kcal/mol. In silico immune simulation predicted robust humoral and cellular immune responses, including sustained memory cell populations following three-dose immunisation. These computational findings support the RVC as a promising broad-spectrum human coronavirus vaccine candidate. However, experimental validation, including immunogenicity, safety and protective efficacy studies in relevant in vitro and in vivo models, is warranted to substantiate its translational applicability.

Matched MeSH terms: Spike Glycoprotein, Coronavirus/immunology
Fulltext Prospective Evaluation of Antibody Response post COVID-19 vaccination in older persons ≧ 60 years old (PEARL 60): A longitudinal 15-months study in a tertiary centre in Malaysia

Hasmukharay K, Verma AK, Aravindhan K, Alagappan PRS, Kamal AKM, Zulhaimi NS, et al.

PLoS One, 2026;21(2):e0340891.
PMID: 41666143 DOI: 10.1371/journal.pone.0340891

Older adults exhibit heterogeneous immune responses to COVID-19 vaccination, yet the relative contributions of age, comorbidity, vaccine platform, and infection history to antibody durability remain incompletely defined. Understanding these determinants is essential to inform booster strategies in ageing populations. We conducted a longitudinal observational study of 300 participants (250 aged ≥60 years and 50 younger controls) followed for up to 15 months. Anti-spike (anti-S) antibody responses were assessed at four event-anchored timepoints: ≤ 3 months post-primary vaccination (TP1), ~ 3 months post-first booster (TP2), 6-9 months post-first booster capturing waning immunity (TP3), and ≤3 months post-second booster where available (TP4). Multivariable log-linear regression models were used to identify independent determinants of antibody levels, with additional analyses stratified by infection status and vaccine platform. Among older adults, 78.8% had moderate-to-severe comorbidity burden, 40.0% were pre-frail, and only 16.8% received a second booster. At TP3, older age was associated with lower antibody levels in univariable analysis (GMR 0.81, 95% CI 0.68-0.97) but not after adjustment (aGMR 0.78, 95% CI 0.51-1.22, p = 0.279). Independent predictors of higher TP3 antibody levels included female sex (aGMR 1.24, 95% CI 1.02-1.51, p = 0.028), prior SARS-CoV-2 infection (aGMR 1.39, 95% CI 1.14-1.71, p = 0.001), and mRNA (aGMR 5.16, 95% CI 3.57-7.47, p=<0.001) or viral vector boosters (aGMR 6.05, 95% CI 4.03-9.08, p=<0.001), while renal disease was associated with lower responses (aGMR 0.71, 95% CI 0.54-0.94, p = 0.017). Similar associations were observed at TP4. Frailty and sarcopenia were not independently associated with antibody levels. Neutralising antibodies against Omicron were absent after primary vaccination and detected in only 25.9% of infection-naïve older adults after the first booster. Sustained humoral immunity following COVID-19 vaccination is driven primarily by vaccine platform and immune history rather than chronological age or geriatric syndromes alone. Waning immunity unmasks vulnerability in older adults, while low uptake of second boosters highlights a critical gap between immunological risk and vaccine utilisation. These findings support targeted, equity-focused booster strategies prioritising highly immunogenic platforms and high-risk older adults.

Matched MeSH terms: Spike Glycoprotein, Coronavirus/immunology
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
Can Costus afer be used for co-treatment of COVID-19, its symptoms and comorbidities? A novel approach for combating the pandemic and implications for sub-Saharan Africa

Jannat K, Hasan A, Bondhon TA, Mahboob T, Paul AK, Jahan R, et al.

Trop Biomed, 2021 Dec 01;38(4):540-551.
PMID: 35001920 DOI: 10.47665/tb.38.4.097

Despite the huge loss of lives and massive disruption of the world economy by the COVID -19 pandemic caused by SARS -CoV-2, scientists are yet to come out with an effective therapeutic against this viral disease . Several vaccines have obtained 'emergency approval ', but difficulties are being faced in the even distribution of vaccines amongst high- and low- income countries . On top of it, comorbidities associated with COVID -19 like diabetes, hypertension and malaria can seriously impede the treatment of the main disease, thus increasing the fatality rate . This is more so in the context of sub -Saharan African and south Asian countries . Our objective was to demonstrate that a single plant containing different phytoconstituents may be used for treatment of COVID -19 and comorbidities . Towards initial selection of a plant, existing scientific literature was scanned for reported relevant traditional uses, phytochemicals and pharmacological activities of a number of plants and their phytoconstituents pertaining to treatment of COVID-19 symptoms and comorbidities. Molecular docking studies were then performed with phytochemicals of the selected plant and SARS-CoV-2 components - Mpro, and spike protein receptor binding domain and hACE2 interface using AutoDock V ina. We showed that crude extracts of an indigenous African plant, Costus afer having traditional antidiabetic and antimalarial uses, has phytochemicals with high binding affinities for Mpro, and /or spike protein receptor binding domain and hACE2 interface; the various phytochemicals with predicted high binding energies include aferoside C, dibutyl phthalate, nerolidol, suginal, and ± -terpinene, making them potential therapeutics for COVID -19. The results suggest that crude extracts and phytochemicals of C. afer can function as a treatment modality for COVID -19 and comorbidities like especially diabetes and malaria .

Matched MeSH terms: Spike Glycoprotein, Coronavirus
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
Fulltext Mixing versus matching booster vaccines: Longitudinal humoral immune kinetics against Omicron in a Malaysian cohort

Thundakattil AV, Prabhu R, Prabhu G, Mani M, De S, Soe HHK, et al.

Int J Infect Dis, 2026 Nov;172:109103.
PMID: 42697472 DOI: 10.1016/j.ijid.2026.109103

OBJECTIVES: The objective of our study was to evaluate the longitudinal humoral immune response following booster regimens in Malaysia during the Omicron outbreak.
METHODS: In this prospective cohort study, 268 healthcare professionals and medical students in Malaysia were followed up for 24 weeks following homologous (messenger ribonucleic acid [mRNA]-mRNA [mR-mR], viral vector-viral vector [VV-VV], inactivated virus-inactivated virus [IV-IV]) and heterologous (inactivated virus-mRNA [IV-mR], viral vector-mRNA [VV-mR]) booster vaccines. Of them, 190 recipients underwent a longitudinal immunogenicity study. Anti-spike (anti-S) immunoglobulin G (IgG) and anti-receptor-binding domain (anti-RBD) responses were assessed by the ADVIA Centaur severe acute respiratory syndrome coronavirus 2 chemiluminescent immunoassay followed by a surrogate virus neutralization test using the Omicron variant across all boosters.
RESULTS: Compared to homologous boosters, heterologous regimens, particularly the IV-mR booster, elicited significantly higher and sustained anti-S IgG and anti-RBD antibody (P < 0.0001) responses. Over 24 weeks, the heterologous IV-mR booster group had 100% seropositivity for anti-S IgG and anti-RBD antibodies; conversely, in the homologous (IV-IV) booster group, the seropositivity of anti-S IgG and anti-RBD antibodies decreased to 15.63% and 18.75%, respectively. Omicron virus-neutralizing was observed to be as high as 95.92% (IV-mR) and 83.87% (VV-mR) at week 24 after the heterologous booster, while virus neutralization was found to be as low as 9.38% in the IV-IV homologous booster. Age, gender, and ethnicity were not found to be confounding factors for antibody kinetics following a booster vaccine.
CONCLUSION: In conclusion, heterologous booster vaccines induced a superior prolonged humoral immune response against coronavirus disease 2019 infection.

Matched MeSH terms: Spike Glycoprotein, Coronavirus/immunology
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*
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
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
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

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