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Fulltext Therapeutic potential of coumarins as antiviral agents

Hassan MZ, Osman H, Ali MA, Ahsan MJ

Eur J Med Chem, 2016 Nov 10;123:236-255.
PMID: 27484512 DOI: 10.1016/j.ejmech.2016.07.056

Coumarins have received a considerable attention in the last three decades as a lead structures for the discovery of orally bioavailable non-peptidic antiviral agents. A lot of structurally diverse coumarins analogues were found to display remarkable array of affinity with the different molecular targets for antiviral agents and slight modifications around the central motif result in pronounced changes in its antiviral spectrum. This manuscript thoroughly reviews the design, discovery and structure-activity relationship studies of the coumarin analogues as antiviral agents focusing mainly on lead optimization and its development into clinical candidates.

Matched MeSH terms: Antiviral Agents/pharmacology*
Fulltext Shaping the future of antiviral Treatment: Spotlight on Nucleobase-Containing drugs and their revolutionary impact

Wong XK, Ng CS, Yeong KY

Bioorg Chem, 2024 Mar;144:107150.
PMID: 38309002 DOI: 10.1016/j.bioorg.2024.107150

Nucleobases serve as essential molecular frameworks present in both natural and synthetic compounds that exhibit notable antiviral activity. Through molecular modifications, novel nucleobase-containing drugs (NCDs) have been developed, exhibiting enhanced antiviral activity against a wide range of viruses, including the recently emerged SARS‑CoV‑2. This article provides a detailed examination of the significant advancements in NCDs from 2015 till current, encompassing various aspects concerning their mechanisms of action, pharmacology and antiviral properties. Additionally, the article discusses antiviral prodrugs relevant to the scope of this review. It fills in the knowledge gap by examining the structure-activity relationship and trend of NCDs as therapeutics against a diverse range of viral diseases, either as approved drugs, clinical candidates or as early-stage development prospects. Moreover, the article highlights on the status of this field of study and addresses the prevailing limitations encountered.

Matched MeSH terms: Antiviral Agents/pharmacology
Fulltext A review on antibacterial, antiviral, and antifungal activity of curcumin

Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K

Biomed Res Int, 2014;2014:186864.
PMID: 24877064 DOI: 10.1155/2014/186864

Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent.

Matched MeSH terms: Antiviral Agents/pharmacology*
Sub-structure-based screening and molecular docking studies of potential enteroviruses inhibitors

James SA, Yam WK

Comput Biol Chem, 2021 Jun;92:107499.
PMID: 33932782 DOI: 10.1016/j.compbiolchem.2021.107499

Rhinoviruses (RV), especially Human rhinovirus (HRVs) have been accepted as the most common cause for upper respiratory tract infections (URTIs). Pleconaril, a broad spectrum anti-rhinoviral compound, has been used as a drug of choice for URTIs for over a decade. Unfortunately, for various complications associated with this drug, it was rejected, and a replacement is highly desirable. In silico screening and prediction methods such as sub-structure search and molecular docking have been widely used to identify alternative compounds. In our study, we have utilised sub-structure search to narrow down our quest in finding relevant chemical compounds. Molecular docking studies were then used to study their binding interaction at the molecular level. Interestingly, we have identified 3 residues that is worth further investigation in upcoming molecular dynamics simulation systems of their contribution in stable interaction.

Matched MeSH terms: Antiviral Agents/pharmacology
Peptide inhibitors of Macrobrachium rosenbergii nodavirus

Thong QX, Wong CL, Ooi MK, Kueh CL, Ho KL, Alitheen NB, et al.

J Gen Virol, 2018 09;99(9):1227-1238.
PMID: 30041713 DOI: 10.1099/jgv.0.001116

Macrobrachium rosenbergii nodavirus (MrNv) causes white tail disease (WTD) in giant freshwater prawns, which leads to devastating economic losses in the aquaculture industry. Despite extensive research on MrNv, there is still no antiviral agent to treat WTD. Thus, the main aim of this study was to identify potential anti-MrNv molecules. A 12-mer phage-displayed peptide library was biopanned against the MrNv virus-like particle (VLP). After four rounds of biopanning, two dominant phages harbouring the amino acid sequences HTKQIPRHIYSA and VSRHQSWHPHDL were selected. An equilibrium binding assay in solution was performed to determine the relative dissociation constant (KDrel) of the interaction between the MrNv VLP and the selected fusion phages. Phage-HTKQIPRHIYSA has a KDrel value of 92.4±22.8 nM, and phage-VSRHQSWHPHDL has a KDrel value of 12.7±3.8 nM. An in-cell elisa was used to determine the inhibitory effect of the synthetic peptides towards the entry of MrNv VLP into Spodoptera frugiperda (Sf9) cells. Peptides HTKQIPRHIYSA and VSRHQSWHPHDL inhibited the entry of the MrNv VLP into Sf9 cells with IC50 values of 30.4±3.6 and 26.5±8.8 µM, respectively. Combination of both peptides showed a significantly higher inhibitory effect with an IC50 of 4.9±0.4 µM. An MTT assay revealed that the viability of MrNv-infected cells increased to about 97 % in the presence of both peptides. A real-time RT-PCR assay showed that simultaneous application of both peptides significantly reduced the number of MrNv per infected cell, from 97±9 to 11±4. These peptides are lead compounds which can be further developed into potent anti-MrNv agents.

Matched MeSH terms: Antiviral Agents/pharmacology*
Fulltext Screening for natural and derived bio-active compounds in preclinical and clinical studies: One of the frontlines of fighting the coronaviruses pandemic

Khalifa SAM, Yosri N, El-Mallah MF, Ghonaim R, Guo Z, Musharraf SG, et al.

Phytomedicine, 2021 May;85:153311.
PMID: 33067112 DOI: 10.1016/j.phymed.2020.153311

BACKGROUND: Starting December 2019, mankind faced an unprecedented enemy, the COVID-19 virus. The world convened in international efforts, experiences and technologies in order to fight the emerging pandemic. Isolation, hygiene measure, diagnosis, and treatment are the most efficient ways of prevention and intervention nowadays. The health organizations and global care systems screened the available resources and offered recommendations of approved and proposed medications. However, the search for a specific selective therapy or vaccine against COVID-19 remains a challenge.
METHODS: A literature search was performed for the screening of natural and derived bio-active compounds which showed potent antiviral activity against coronaviruses using published articles, patents, clinical trials website (https://clinicaltrials.gov/) and web databases (PubMed, SCI Finder, Science Direct, and Google Scholar).
RESULTS: Through the screening for natural products with antiviral activities against different types of the human coronavirus, extracts of Lycoris radiata (L'Hér.), Gentiana scabra Bunge, Dioscorea batatas Decne., Cassia tora L., Taxillus chinensis (DC.), Cibotium barometz L. and Echinacea purpurea L. showed a promising effect against SARS-CoV. Out of the listed compound Lycorine, emetine dihydrochloride hydrate, pristimerin, harmine, conessine, berbamine, 4`-hydroxychalcone, papaverine, mycophenolic acid, mycophenolate mofetil, monensin sodium, cycloheximide, oligomycin and valinomycin show potent activity against human coronaviruses. Additionally, it is worth noting that some compounds have already moved into clinical trials for their activity against COVID-19 including fingolimod, methylprednisolone, chloroquine, tetrandrine and tocilizumab.
CONCLUSION: Natural compounds and their derivatives could be used for developing potent therapeutics with significant activity against SARS-COV-2, providing a promising frontline in the fighting against COVID-19.

Matched MeSH terms: Antiviral Agents/pharmacology*
Fulltext Chemical composition, antioxidant, antimicrobial and antiviral activities of the leaf extracts of Syzygium myrtifolium

Ahmad MA, Lim YH, Chan YS, Hsu CY, Wu TY, Sit NW

Acta Pharm, 2022 Jun 01;72(2):317-328.
PMID: 36651512 DOI: 10.2478/acph-2022-0013

This study was conducted to evaluate the chemical composition and biological activities of the leaf extracts of Syzygium myrtifolium Walp. (Myrtaceae). The results indicate that the leaf extracts of S. myrtifolium contain various classes of phytochemicals (alkaloids, anthraquinones, flavonoids, phenolics, saponins, tannins and triterpenoids) and possess antioxidant, antibacterial, antifungal and antiviral activities. Ethyl acetate, ethanol, methanol, and water extracts exhibited significantly higher (p < 0.05) oxygen radical absorbance capacity and ferric-reducing antioxidant power than the hexane and chloroform extracts. However, all extracts exhibited stronger inhibitory activity against four tested species of yeasts (minimal inhibitory concentration: 0.02-0.31 mg mL-1) than against six tested species of bacteria (minimal inhibitory concentration: 0.16-1.25 mg mL-1). The ethanolic extract offered the highest protection of Vero cells (viability > 70 %) from the cytopathic effect caused by the Chikungunya virus while the ethyl acetate extract showed significant replication inhibitory activity against the virus (p < 0.001) using the replicon-enhanced green fluorescent protein reporter system.

Matched MeSH terms: Antiviral Agents/pharmacology
Fulltext Contemporary Approaches to the Discovery and Development of Broad-Spectrum Natural Product Prototypes for the Control of Coronaviruses

Hanna GS, Choo YM, Harbit R, Paeth H, Wilde S, Mackle J, et al.

J Nat Prod, 2021 Nov 26;84(11):3001-3007.
PMID: 34677966 DOI: 10.1021/acs.jnatprod.1c00625

The pressing need for SARS-CoV-2 controls has led to a reassessment of strategies to identify and develop natural product inhibitors of zoonotic, highly virulent, and rapidly emerging viruses. This review article addresses how contemporary approaches involving computational chemistry, natural product (NP) and protein databases, and mass spectrometry (MS) derived target-ligand interaction analysis can be utilized to expedite the interrogation of NP structures while minimizing the time and expense of extraction, purification, and screening in BioSafety Laboratories (BSL)3 laboratories. The unparalleled structural diversity and complexity of NPs is an extraordinary resource for the discovery and development of broad-spectrum inhibitors of viral genera, including Betacoronavirus, which contains MERS, SARS, SARS-CoV-2, and the common cold. There are two key technological advances that have created unique opportunities for the identification of NP prototypes with greater efficiency: (1) the application of structural databases for NPs and target proteins and (2) the application of modern MS techniques to assess protein-ligand interactions directly from NP extracts. These approaches, developed over years, now allow for the identification and isolation of unique antiviral ligands without the immediate need for BSL3 facilities. Overall, the goal is to improve the success rate of NP-based screening by focusing resources on source materials with a higher likelihood of success, while simultaneously providing opportunities for the discovery of novel ligands to selectively target proteins involved in viral infection.

Matched MeSH terms: Antiviral Agents/pharmacology*
Fighting nature with nature: antiviral compounds that target retroviruses

Siew ZY, Asudas E, Khoo CT, Cho GH, Voon K, Fang CM

Arch Microbiol, 2024 Feb 28;206(3):130.
PMID: 38416180 DOI: 10.1007/s00203-024-03846-3

The human immunodeficiency virus (HIV) is a type of lentivirus that targets the human immune system and leads to acquired immunodeficiency syndrome (AIDS) at a later stage. Up to 2021, there are millions still living with HIV and many have lost their lives. To date, many anti-HIV compounds have been discovered in living organisms, especially plants and marine sponges. However, no treatment can offer a complete cure, but only suppressing it with a life-long medication, known as combined antiretroviral therapy (cART) or highly active antiretroviral therapy (HAART) which are often associated with various adverse effects. Also, it takes many years for a discovered compound to be approved for clinical use. Thus, by employing advanced technologies such as automation, conducting systematic screening and testing protocols may boost the discovery and development of potent and curative therapeutics for HIV infection/AIDS. In this review, we aim to summarize the antiretroviral therapies/compounds and their associated drawbacks since the discovery of azidothymidine. Additionally, we aim to provide an updated analysis of the most recent discoveries of promising antiretroviral candidates, along with an exploration of the current limitations within antiretroviral research. Finally, we intend to glean insightful perspectives and propose future research directions in this crucial area of study.

Matched MeSH terms: Antiviral Agents/pharmacology
Fulltext Viral Protein Accumulation of Zika Virus Variants Links with Regulation of Innate Immunity for Differential Control of Viral Replication, Spread, and Response to Interferon

Lu AY, Gustin A, Newhouse D, Gale M

J Virol, 2023 May 31;97(5):e0198222.
PMID: 37162358 DOI: 10.1128/jvi.01982-22

Asian lineage Zika virus (ZIKV) strains emerged globally, causing outbreaks linked with critical clinical disease outcomes unless the virus is effectively restricted by host immunity. We have previously shown that retinoic acid-inducible gene-I (RIG-I) senses ZIKV to trigger innate immunity to direct interferon (IFN) production and antiviral responses that can control ZIKV infection. However, ZIKV proteins have been demonstrated to antagonize IFN. Here, we conducted in vitro analyses to assess how divergent prototypic ZIKV variants differ in virologic properties, innate immune regulation, and infection outcome. We comparatively assessed African lineage ZIKV/Dakar/1984/ArD41519 (ZIKV/Dakar) and Asian lineage ZIKV/Malaysia/1966/P6740 (ZIKV/Malaysia) in a human epithelial cell infection model. De novo viral sequence determination identified amino acid changes within the ZIKV/Dakar genome compared to ZIKV/Malaysia. Viral growth analyses revealed that ZIKV/Malaysia accumulated viral proteins and genome copies earlier and to higher levels than ZIKV/Dakar. Both ZIKV strains activated RIG-I/IFN regulatory factor (IRF3) and NF-κB pathways to induce inflammatory cytokine expression and types I and III IFNs. However, ZIKV/Malaysia, but not ZIKV/Dakar, potently blocked downstream IFN signaling. Remarkably, ZIKV/Dakar protein accumulation and genome replication were rescued in RIG-I knockout (KO) cells late in acute infection, resulting in ZIKV/Dakar-mediated blockade of IFN signaling. We found that RIG-I signaling specifically restricts viral protein accumulation late in acute infection where early accumulation of viral proteins in infected cells confers enhanced ability to limit IFN signaling, promoting viral replication and spread. Our results demonstrate that RIG-I-mediated innate immune signaling imparts restriction of ZIKV protein accumulation, which permits IFN signaling and antiviral actions controlling ZIKV infection. IMPORTANCE ZIKV isolates are classified under African or Asian lineages. Infection with emerging Asian lineage-derived ZIKV strains is associated with increased incidence of neurological symptoms that were not previously reported during infection with African or preemergent Asian lineage viruses. In this study, we utilized in vitro models to compare the virologic properties of and innate immune responses to two prototypic ZIKV strains from distinct lineages: African lineage ZIKV/Dakar and Asian lineage ZIKV/Malaysia. Compared to ZIKV/Dakar, ZIKV/Malaysia accumulates viral proteins earlier, replicates to higher levels, and robustly blocks IFN signaling during acute infection. Early accumulation of ZIKV/Malaysia NS5 protein confers enhanced ability to antagonize IFN signaling, dampening innate immune responses to promote viral spread. Our data identify the kinetics of viral protein accumulation as a major regulator of host innate immunity, influencing host-mediated control of ZIKV replication and spread. Importantly, these findings provide a novel framework for evaluating the virulence of emerging variants.

Matched MeSH terms: Antiviral Agents/pharmacology
Discovery of plant-based phytochemical as effective antivirals that target the non-structural protein C of the Nipah virus through computational methods

Sureshan M, Prabhu D, Joshua SN, Sasikumar SV, Rajamanikandan S, Govindhapriya M, et al.

J Biomol Struct Dyn, 2024 Apr;42(7):3568-3578.
PMID: 37222609 DOI: 10.1080/07391102.2023.2214236

Nipah Virus (NiV) belongs to the Paramyxoviridae family and was first identified during an outbreak in Malaysia. Some initial symptoms include mild fever, headache and sore throat, which could escalate to respiratory illness and brain inflammation. The mortality rate of NiV infection can range from 40% to 75%, which is quite high. This is mainly due to the lack of efficient drugs and vaccines. In most instances, NiV is transmitted from animals to humans. Non-Structural Proteins (C, V and W) of the Nipah virus impede the host immune response by obstructive the JAK/STAT pathway. However, Non-Structural Proteins - C (NSP-C) plays a vital role in NiV pathogenesis, which includes IFN antagonist activity and viral RNA production. In the present study, the full-length structure of NiV-NSP-C was predicted using computational modelling, and the stability of the structure was analysed using 200 ns molecular dynamic (MD) simulation. Further, the structure-based virtual screening identified five potent phytochemicals (PubChem CID: 9896047, 5885, 117678, 14887603 and 5461026) with better binding affinity against NiV-NSP-C. DFT studies clearly showed that the phytochemicals had higher chemical reactivity, and the complex MD simulation depicted that the identified inhibitors exhibited stable binding with NiV-NSP-C. Furthermore, experimental validation of these identified phytochemicals would likely control the infection of NiV.Communicated by Ramaswamy H. Sarma.

Matched MeSH terms: Antiviral Agents/pharmacology
Inhibitory effect of doxycycline against dengue virus replication in vitro

Rothan HA, Mohamed Z, Paydar M, Rahman NA, Yusof R

Arch Virol, 2014 Apr;159(4):711-8.
PMID: 24142271 DOI: 10.1007/s00705-013-1880-7

Doxycycline is an antibiotic derived from tetracycline that possesses antimicrobial and anti-inflammatory activities. Antiviral activity of doxycycline against dengue virus has been reported previously; however, its anti-dengue properties need further investigation. This study was conducted to determine the potential activity of doxycycline against dengue virus replication in vitro. Doxycycline inhibited the dengue virus serine protease (DENV2 NS2B-NS3pro) with an IC50 value of 52.3 ± 6.2 μM at 37 °C (normal human temperature) and 26.7 ± 5.3 μM at 40 °C (high fever temperature). The antiviral activity of doxycycline was first tested at different concentrations against DENV2 using a plaque-formation assay. The virus titter decreased significantly after applying doxycycline at levels lower than its 50 % cytotoxic concentration (CC50, 100 μM), showing concentration-dependent inhibition with a 50 % effective concentration (EC50) of approximately 50 μM. Doxycycline significantly inhibited viral entry and post-infection replication of the four dengue serotypes, with serotype-specific inhibition (high activity against DENV2 and DENV4 compared to DENV1 and DENV3). Collectively, these findings underline the need for further experimental and clinical studies on doxycycline, utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue virus infection.

Matched MeSH terms: Antiviral Agents/pharmacology*
Fulltext Potential anti-dengue medicinal plants: a review

Abd Kadir SL, Yaakob H, Mohamed Zulkifli R

J Nat Med, 2013 Oct;67(4):677-89.
PMID: 23591999 DOI: 10.1007/s11418-013-0767-y

Dengue fever causes mortality and morbidity around the world, specifically in the Tropics and subtropic regions, which has been of major concern to governments and the World Health Organization (WHO). As a consequence, the search for new anti-dengue agents from medicinal plants has assumed more urgency than in the past. Medicinal plants have been used widely to treat a variety of vector ailments such as malaria. The demand for plant-based medicines is growing as they are generally considered to be safer, non-toxic and less harmful than synthetic drugs. This article reviews potential anti-dengue activities from plants distributed around the world. Sixty-nine studies from 1997 to 2012 describe 31 different species from 24 families that are known for their anti-dengue activities. About ten phytochemicals have been isolated from 11 species, among which are compounds with the potential for development of dengue treatment. Crude extracts and essential oils obtained from 31 species showed a broad activity against Flavivirus. Current studies show that natural products represent a rich potential source of new anti-dengue compounds. Further ethnobotanical surveys and laboratory investigations are needed established the potential of identified species in contributing to dengue control.

Matched MeSH terms: Antiviral Agents/pharmacology
Fulltext Design, synthesis and antiviral potential of 14-aryl/heteroaryl-14H-dibenzo[a,j]xanthenes using an efficient polymer-supported catalyst

Reddi Mohan Naidu K, Satheesh Krishna B, Anil Kumar M, Arulselvan P, Ibrahim Khalivulla S, Lasekan O

Molecules, 2012 Jun 18;17(6):7543-55.
PMID: 22710828 DOI: 10.3390/molecules17067543

Polyethyleneglycol bound sulfonic acid (PEG-OSO₃H), a chlorosulphonic acid-modified polyethylene glycol was successfully used as an efficient and eco-friendly polymeric catalyst in the synthesis of 14-aryl/heteroaryl-14H-dibenzo[a,j]xanthenes obtained from the reaction of 2-naphthol and carbonyl compounds under solvent-free conditions with short reaction times and excellent yields. The biological properties of these synthesized title compounds revealed that compounds 3b, 3c, 3f and 3i showed highly significant anti-viral activity against tobacco mosaic virus.

Matched MeSH terms: Antiviral Agents/pharmacology*
Fulltext Identification and characterisation of a novel anti-viral peptide against avian influenza virus H9N2

Rajik M, Jahanshiri F, Omar AR, Ideris A, Hassan SS, Yusoff K

Virol J, 2009;6:74.
PMID: 19497129 DOI: 10.1186/1743-422X-6-74

Avian influenza viruses (AIV) cause high morbidity and mortality among the poultry worldwide. Their highly mutative nature often results in the emergence of drug resistant strains, which have the potential of causing a pandemic. The virus has two immunologically important glycoproteins, hemagglutinin (HA), neuraminidase (NA), and one ion channel protein M2 which are the most important targets for drug discovery, on its surface. In order to identify a peptide-based virus inhibitor against any of these surface proteins, a disulfide constrained heptapeptide phage display library was biopanned against purified AIV sub-type H9N2 virus particles.

Matched MeSH terms: Antiviral Agents/pharmacology*
Antiviral properties of ent-labdene diterpenes of Andrographis paniculata nees, inhibitors of herpes simplex virus type 1

Wiart C, Kumar K, Yusof MY, Hamimah H, Fauzi ZM, Sulaiman M

Phytother Res, 2005 Dec;19(12):1069-70.
PMID: 16372376

Andrographolide, neoandrographolide and 14-deoxy-11,12-didehydroandrographolide, ent-labdene diterpenes isolated from Andrographis paniculata showed viricidal activity against herpes simplex virus 1 (HSV-1). None of these compounds exhibited significant cytotoxicity at viricidal concentrations.

Matched MeSH terms: Antiviral Agents/pharmacology*
Chronic hepatitis B and herbal therapy

Shahidah KN, Merican I

Med J Malaysia, 2005 Jul;60 Suppl B:35-8.
PMID: 16108171
Matched MeSH terms: Antiviral Agents/pharmacology
Fulltext Antiviral Potential of Algae Polysaccharides Isolated from Marine Sources: A Review

Ahmadi A, Zorofchian Moghadamtousi S, Abubakar S, Zandi K

Biomed Res Int, 2015;2015:825203.
PMID: 26484353 DOI: 10.1155/2015/825203

From food to fertilizer, algal derived products are largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. Among different chemical compositions isolated from algae, polysaccharides are the most well-established compounds, which were subjected to a variety of studies due to extensive bioactivities. Over the past few decades, the promising results for antiviral potential of algae-derived polysaccharides have advocated them as inordinate candidates for pharmaceutical research. Numerous studies have isolated various algal polysaccharides possessing antiviral activities, including carrageenan, alginate, fucan, laminaran, and naviculan. In addition, different mechanisms of action have been reported for these polysaccharides, such as inhibiting the binding or internalization of virus into the host cells or suppressing DNA replication and protein synthesis. This review strives for compiling previous antiviral studies of algae-derived polysaccharides and their mechanism of action towards their development as natural antiviral agents for future investigations.

Matched MeSH terms: Antiviral Agents/pharmacology*
A Real-Time Cell Analyzing Assay for Identification of Novel Antiviral Compounds against Chikungunya Virus

Zandi K

Methods Mol Biol, 2016;1426:255-62.
PMID: 27233278 DOI: 10.1007/978-1-4939-3618-2_23

Screening of viral inhibitors through induction of cytopathic effects (CPE) by conventional method has been applied for various viruses including Chikungunya virus (CHIKV), a significant arbovirus. However, it does not provide the information about cytopathic effect from the beginning and throughout the course of virus replication. Conventionally, most of the approaches are constructed on laborious end-point assays which are not capable for detecting minute and rapid changes in cellular morphology. Therefore, we developed a label-free and dynamical method for monitoring the cellular features that comprises cell attachment, proliferation, and viral cytopathogenicity, known as the xCELLigence real-time cell analysis (RTCA). In this chapter, we provide a RTCA protocol for quantitative analysis of CHIKV replication using an infected Vero cell line treated with ribavirin as an in vitro model.

Matched MeSH terms: Antiviral Agents/pharmacology*
Vitamin D is a potential inhibitor of COVID-19: In silico molecular docking to the binding site of SARS-CoV-2 endoribonuclease Nsp15

Shalayel MH, Al-Mazaideh GM, Aladaileh SH, Al-Swailmi FK, Al-Thiabat MG

Pak J Pharm Sci, 2020 Sep;33(5):2179-2186.
PMID: 33824127

Novel coronavirus disease (COVID-19) has become a pandemic threat to public health. Vaccines and targeted therapeutics to prevent infections and stop virus proliferation are currently lacking. Endoribonuclease Nsp15 plays a vital role in the life cycle, including replication and transcription as well as virulence of the virus. Here, we investigated Vitamin D for its in silico potential inhibition of the binding sites of SARS-CoV-2 endoribonuclease Nsp15. In this study, we selected Remdesivir, Chloroquine, Hydroxychloroquine and Vitamin D to study the potential binding affinity with the putative binding sites of endoribonuclease Nsp15 of COVID-19. The docking study was applied to rationalize the possible interactions of the target compounds with the active site of endoribonuclease Nsp 15. Among the results, Vitamin D was found to have the highest potency with strongest interaction in terms of LBE, lowest RMSD, and lowest inhibition intensity Ki than the other standard compounds. The investigation results of endoribonuclease Nsp15 on the PrankWeb server showed that there are three prospective binding sites with the ligands. The singularity of Vitamin D interaction with the three pockets, particularly in the second pocket, may write down Vitamin D as a potential inhibitor of COVID-19 Nsp15 endoribonuclease binding sites and favour addition of Vitamin D in the treatment plan for COVID-19 alone or in combination with the other used drugs in this purpose, which deserves exploration in further in vitro and in vivo studies.

Matched MeSH terms: Antiviral Agents/pharmacology

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