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Viruses ; 13(8)2021 08 23.
Article in English | MEDLINE | ID: covidwho-1524167


The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread despite the global efforts taken to control it. The 3C-like protease (3CLpro), the major protease of SARS-CoV-2, is one of the most interesting targets for antiviral drug development because it is highly conserved among SARS-CoVs and plays an important role in viral replication. Herein, we developed high throughput screening for SARS-CoV-2 3CLpro inhibitor based on AlphaScreen. We screened 91 natural product compounds and found that all-trans retinoic acid (ATRA), an FDA-approved drug, inhibited 3CLpro activity. The 3CLpro inhibitory effect of ATRA was confirmed in vitro by both immunoblotting and AlphaScreen with a 50% inhibition concentration (IC50) of 24.7 ± 1.65 µM. ATRA inhibited the replication of SARS-CoV-2 in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 = 2.69 ± 0.09 µM in the former and 0.82 ± 0.01 µM in the latter. Further, we showed the anti-SARS-CoV-2 effect of ATRA on the currently circulating variants of concern (VOC); alpha, beta, gamma, and delta. These results suggest that ATRA may be considered as a potential therapeutic agent against SARS-CoV-2.

Antiviral Agents/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , SARS-CoV-2/drug effects , Tretinoin/pharmacology , Animals , Cell Line, Tumor , Chlorocebus aethiops , Cysteine Proteinase Inhibitors/pharmacology , DEAD Box Protein 58/metabolism , High-Throughput Screening Assays , Humans , Receptors, Immunologic/metabolism , SARS-CoV-2/enzymology , SARS-CoV-2/physiology , Vero Cells , Virus Replication/drug effects
Cell Rep Med ; 2(6): 100311, 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1230816


The ongoing coronavirus disease 2019 (COVID-19) pandemic is a major global public health concern. Although rapid point-of-care testing for detecting viral antigen is important for management of the outbreak, the current antigen tests are less sensitive than nucleic acid testing. In our current study, we produce monoclonal antibodies (mAbs) that exclusively react with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and exhibit no cross-reactivity with other human coronaviruses, including SARS-CoV. Molecular modeling suggests that the mAbs bind to epitopes present on the exterior surface of the nucleocapsid, making them suitable for detecting SARS-CoV-2 in clinical samples. We further select the optimal pair of anti-SARS-CoV-2 nucleocapsid protein (NP) mAbs using ELISA and then use this mAb pair to develop immunochromatographic assay augmented with silver amplification technology. Our mAbs recognize the variants of concern (501Y.V1-V3) that are currently in circulation. Because of their high performance, the mAbs of this study can serve as good candidates for developing antigen detection kits for COVID-19.

Biochem Biophys Res Commun ; 533(1): 195-200, 2020 11 26.
Article in English | MEDLINE | ID: covidwho-753910


The pandemic of COVID-19 is spreading unchecked due to the lack of effective antiviral measures. Silver nanoparticles (AgNP) have been studied to possess antiviral properties and are presumed to inhibit SARS-CoV-2. Due to the need for an effective agent against SARS-CoV-2, we evaluated the antiviral effect of AgNPs. We evaluated a plethora of AgNPs of different sizes and concentration and observed that particles of diameter around 10 nm were effective in inhibiting extracellular SARS-CoV-2 at concentrations ranging between 1 and 10 ppm while cytotoxic effect was observed at concentrations of 20 ppm and above. Luciferase-based pseudovirus entry assay revealed that AgNPs potently inhibited viral entry step via disrupting viral integrity. These results indicate that AgNPs are highly potent microbicides against SARS-CoV-2 but should be used with caution due to their cytotoxic effects and their potential to derange environmental ecosystems when improperly disposed.

Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Metal Nanoparticles/administration & dosage , Pneumonia, Viral/drug therapy , Silver/administration & dosage , Animals , Antiviral Agents/toxicity , Betacoronavirus/physiology , COVID-19 , Cell Line , Cell Survival/drug effects , Chlorocebus aethiops , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Dose-Response Relationship, Drug , Humans , Metal Nanoparticles/toxicity , Metal Nanoparticles/ultrastructure , Pandemics , Particle Size , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Silver/toxicity , Vero Cells , Virus Internalization/drug effects