Small molecules in the treatment of COVID-19

S Lei, X Chen, J Wu, X Duan, K Men - Signal transduction and targeted …, 2022 - nature.com
The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to
societies and economies. Until now, effective therapeutics against COVID-19 are in high …

Structural biology of SARS-CoV-2 Mpro and drug discovery

Y Duan, H Wang, Z Yuan, H Yang - Current Opinion in Structural Biology, 2023 - Elsevier
Since its outbreak in late 2019, the COVID-19 pandemic has drawn enormous attention
worldwide as a consequence of being the most disastrous infectious disease in the past …

Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir

Y Hu, EM Lewandowski, H Tan, X Zhang… - ACS Central …, 2023 - ACS Publications
The SARS-CoV-2 main protease (Mpro) is the drug target of Pfizer's oral drug nirmatrelvir.
The emergence of SARS-CoV-2 variants with mutations in Mpro raised the alarm of potential …

In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir

M Kiso, S Yamayoshi, S Iida, Y Furusawa… - Nature …, 2023 - nature.com
Ensitrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro or
Nsp5), is clinically useful against SARS-CoV-2 including its omicron variants. Since most …

In vitro selection and analysis of SARS-CoV-2 nirmatrelvir resistance mutations contributing to clinical virus resistance surveillance

Y Zhu, I Yurgelonis, S Noell, Q Yang, S Guan, Z Li… - Science …, 2024 - science.org
To facilitate the detection and management of potential clinical antiviral resistance, in vitro
selection of drug-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) …

Fitness effects of mutations to SARS-CoV-2 proteins

JD Bloom, RA Neher - Virus Evolution, 2023 - academic.oup.com
Abstract Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform
assessment of new variants, design of therapeutics resistant to escape, and understanding …

In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir

M Kiso, Y Furusawa, R Uraki, M Imai… - Nature …, 2023 - nature.com
Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is
clinically useful against infection with SARS-CoV-2 including its omicron variants. Since …

Global prevalence of SARS-CoV-2 3CL protease mutations associated with nirmatrelvir or ensitrelvir resistance

JD Ip, AWH Chu, WM Chan, RCY Leung… - …, 2023 - thelancet.com
Summary Background Nirmatrelvir-ritonavir (Paxlovid) and ensitrelvir are 3-chymotrypsin-
like cysteine protease (3CL pro) inhibitors which have been approved for the treatment of …

Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA. 1 variant through NSP6

TY Taha, IP Chen, JM Hayashi, T Tabata… - Nature …, 2023 - nature.com
Abstract Although the SARS-CoV-2 Omicron variant (BA. 1) spread rapidly across the world
and effectively evaded immune responses, its viral fitness in cell and animal models was …

Alkyne derivatives of SARS-CoV-2 main protease inhibitors including nirmatrelvir inhibit by reacting covalently with the Nucleophilic Cysteine

L Brewitz, L Dumjahn, Y Zhao, CD Owen… - Journal of Medicinal …, 2023 - ACS Publications
Nirmatrelvir (PF-07321332) is a nitrile-bearing small-molecule inhibitor that, in combination
with ritonavir, is used to treat infections by severe acute respiratory syndrome coronavirus-2 …