Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern

Antiviral Research, Journal Year: 2022, Volume and Issue: 198, P. 105252 - 105252

Published: Jan. 24, 2022

We assessed the in vitro antiviral activity of remdesivir and its parent nucleoside GS-441524, molnupiravir EIDD-1931 viral protease inhibitor nirmatrelvir against ancestral SARS-CoV2 strain five variants concern including Omicron. VeroE6-GFP cells were pre-treated overnight with serial dilutions compounds before infection. The GFP signal was determined by high-content imaging on day 4 post-infection. All molecules have equipotent virus VOCs Alpha, Beta, Gamma, Delta These findings are line observation that target proteins these antivirals (respectively RNA dependent polymerase main Mpro) highly conserved.

Language: Английский

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The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 15, 2022

Abstract There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally in clinical development. We here report PF-332 exerts equipotent vitro activity four SARS-CoV-2 variants concerns (VoC) it completely arrest replication alpha variant primary human airway epithelial cells grown at air-liquid interface. Treatment Syrian Golden hamsters with (250 mg/kg, twice daily) protected animals intranasal infection beta (B.1.351) delta (B.1.617.2) variants. Moreover, treatment infected prevented transmission to untreated co-housed sentinels.

Language: Английский

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Molnupiravir and Its Antiviral Activity Against COVID-19

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 4, 2022

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) constitutes a major worldwide public health threat and economic burden. is still ongoing the SARS-CoV-2 variants are emerging constantly, resulting in an urgent demand for new drugs to treat this disease. Molnupiravir, biological prodrug of NHC (β-D-N(4)-hydroxycytidine), novel nucleoside analogue with broad-spectrum antiviral activity against SARS-CoV, SARS-CoV-2, Middle East (MERS-CoV), influenza virus, syncytial virus (RSV), bovine viral diarrhea (BVDV), hepatitis C (HCV) Ebola (EBOV). Molnupiravir showed potent therapeutic prophylactic multiple coronaviruses including MERS-CoV animal models. In clinical trials, molnupiravir beneficial effects mild moderate COVID-19 patients favorable safety profile. oral bioavailability highlight its potential utility as candidate COVID-19. This review presents research progress starting discovery synthesis, effects, mechanism. addition, preclinical studies, resistance, safety, drug tolerability also summarized discussed, aiming expand our knowledge on better deal epidemic.

Language: Английский

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Accelerating antiviral drug discovery: lessons from COVID-19

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(7), P. 585 - 603

Published: May 12, 2023

Language: Английский

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A coronavirus assembly inhibitor that targets the viral membrane protein

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

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RdRp inhibitors and COVID-19: Is molnupiravir a good option?

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 146, P. 112517 - 112517

Published: Dec. 9, 2021

Rapid changes in the viral genome allow viruses to evade threats posed by host immune response or antiviral drugs, and can lead persistence cells. RNA-dependent RNA polymerase (RdRp) is an essential enzyme viruses, which involved synthesis through formation of phosphodiester bonds. Therefore, infections such as SARS-CoV-2, RdRp could be a crucial therapeutic target. The present review discusses promising application inhibitors, previously approved currently being tested human clinical trials, treatment virus infections. Nucleoside inhibitors (NIs) bind active site RdRp, while nonnucleoside (NNIs) allosteric sites. Given absence highly effective drugs for COVID-19, discovery efficient this pandemic urgent concern researchers around world. We evidence molnupiravir (MK-4482, EIDD-2801), drug originally designed Alphavirus infections, potential preventive agent management COVID-19. At beginning pandemic, was preclinical development seasonal influenza. When COVID-19 spread dramatically, timeline accelerated focus on pandemic. Real time consultation with regulators took place expedite program. summarize highlight new small molecule treatment.

Language: Английский

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Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants

Antimicrobial Agents and Chemotherapy, Journal Year: 2022, Volume and Issue: 66(6)

Published: May 9, 2022

Genetic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence and rapid spread multiple variants throughout pandemic, which Omicron is currently predominant variant circulating worldwide. SARS-CoV-2 concern/variants interest (VOC/VOI) have evidence increased viral transmission, disease severity, or decreased effectiveness vaccines neutralizing antibodies. Remdesivir (RDV [VEKLURY]) a nucleoside analog prodrug first FDA-approved antiviral treatment COVID-19. Here, we present comprehensive activity assessment RDV its parent nucleoside, GS-441524, against 10 current former VOC/VOI clinical isolates by nucleoprotein enzyme-linked immunosorbent assay (ELISA) plaque reduction assay. Delta remained susceptible to with 50% effective concentration (EC50) values 0.30- 0.62-fold those observed ancestral WA1 isolate. All other tested exhibited EC50 ranging from 0.13- 2.3-fold WA1. Analysis nearly 6 million publicly available isolate sequences confirmed that Nsp12, RNA-dependent RNA polymerase (RdRp) target highly conserved across variants, only prevalent changes (P323L G671S). Using recombinant viruses, both GS-441524 retained potency all viruses containing frequent substitutions their combination. Taken together, these results highlight nature Nsp12 provide sustained variants. The pan-variant supports continued use for COVID-19 regardless variant.

Language: Английский

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Anatomical barriers against SARS-CoV-2 neuroinvasion at vulnerable interfaces visualized in deceased COVID-19 patients

Neuron, Journal Year: 2022, Volume and Issue: 110(23), P. 3919 - 3935.e6

Published: Nov. 10, 2022

Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct short route from nose into brain? We reasoned that neurotropic or neuroinvasive capacity of virus, if it exists, should be most easily detectable in individuals who died an acute phase infection. Here, we applied postmortem bedside surgical procedure for rapid procurement tissue, blood, cerebrospinal fluid samples deceased COVID-19 patients infected with Delta, Omicron BA.1, BA.2 variants. Confocal imaging sections stained fluorescence RNAscope immunohistochemistry afforded light-microscopic visualization extracellular virions tissues. failed to find evidence viral invasion parenchyma bulb frontal lobe brain. Instead, identified anatomical barriers at vulnerable interfaces, exemplified by perineurial nerve fibroblasts enwrapping axon fascicles lamina propria mucosa.

Language: Английский

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Choosing a cellular model to study SARS-CoV-2

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 21, 2022

As new pathogens emerge, challenges must be faced. This is no different in infectious disease research, where identifying the best tools available laboratories to conduct an investigation can, at least initially, particularly complicated. However, context of emerging virus, such as SARS-CoV-2, which was recently detected China and has become a global threat healthcare systems, developing models infection pathogenesis urgently required. Cell-based approaches are crucial understanding coronavirus biology, growth kinetics, tropism. Usually, laboratory cell lines first line experimental study viral pathogenicity perform assays aimed screening antiviral compounds efficient blocking replication viruses, saving time resources, reducing use animals. determining ideal type can challenging, especially when several researchers have adapt their studies specific requirements. review strives guide scientists who venturing into studying SARS-CoV-2 help them choose right cellular models. It revisits basic concepts virology presents currently

Language: Английский

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Broad‐spectrum prodrugs with anti‐SARS‐CoV‐2 activities: Strategies, benefits, and challenges

Journal of Medical Virology, Journal Year: 2021, Volume and Issue: 94(4), P. 1373 - 1390

Published: Dec. 13, 2021

In this era, broad-spectrum prodrugs with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activities are gaining considerable attention owing to their potential clinical benefits and role in combating the fast-spreading disease 2019 (COVID-19) pandemic. The last years have seen a surge of reports on various against SARS-CoV-2, vitro studies, animal models, practice. Currently, only remdesivir (with many controversies limitations) has been approved by U.S. FDA for treatment SARS-CoV-2 infection, additional potent anti-SARS-CoV-2 drugs urgently required enrich defense arsenals. world ubiquitously grappled COVID-19 pandemic, availability provides great hope us subdue global threat. This article reviews promising strategies, antiviral mechanisms, benefits, daunting challenges agents provide some important guidance future treatment.

Language: Английский

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