tetano
Editor, Senior Moderator
Biochem Biophys Res Commun
. 2023 Jan 14;645:132-136.
doi: 10.1016/j.bbrc.2023.01.040. Online ahead of print.
Ensitrelvir is effective against SARS-CoV-2 3CL protease mutants circulating globally
Sho Kawashima[SUP] 1 [/SUP], Yuki Matsui[SUP] 2 [/SUP], Takumi Adachi[SUP] 2 [/SUP], Yuji Morikawa[SUP] 2 [/SUP], Kae Inoue[SUP] 3 [/SUP], Shiori Takebayashi[SUP] 3 [/SUP], Haruaki Nobori[SUP] 1 [/SUP], Masatomo Rokushima[SUP] 2 [/SUP], Yuki Tachibana[SUP] 4 [/SUP], Teruhisa Kato[SUP] 5 [/SUP]
Affiliations
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a public health concern worldwide. Ensitrelvir (S-217622) has been evaluated as an antiviral treatment for COVID-19, targeting SARS-CoV-2 3C-like protease (3CL[SUP]pro[/SUP]). Ensitrelvir has been reported to have comparable antiviral activity against some of the SARS-CoV-2 variants: alpha, beta, gamma, delta, and omicron (BA.1.18). In this paper, we describe that ensitrelvir is effective against newly emerging SARS-CoV-2 variants and globally prevalent 3CL[SUP]pro[/SUP] mutations. Ensitrelvir exhibited comparable antiviral activity against SARS-CoV-2 variants, including recently emerging ones: omicron (BA1.1, BA.2, BA.2.75, BA.4, BA.5, BQ.1.1, XBB.1, and XE), mu, lambda, and theta. Genetic surveillance of SARS-CoV-2 3CL[SUP]pro[/SUP], the target of ensitrelvir, was conducted using a public database and identified 11 major 3CL[SUP]pro[/SUP] mutations circulating globally (G15S, T21I, T24I, K88R, L89F, K90R, P108S, P132H, A193V, H246Y, and A255V). The 3CL[SUP]pro[/SUP] mutation from proline to histidine at amino acid position 132 was especially identified in the omicron variant, with prevalence of 99.69%. Enzyme kinetic assay revealed that these 3CL[SUP]pro[/SUP] mutants have enzymatic activity comparable to that of the wild type (WT). Next, we assessed the inhibitory effect of ensitrelvir against mutated 3CL[SUP]pro[/SUP], with it showing inhibitory effects similar to that against the WT. These in vitro data suggest that ensitrelvir will be effective against currently circulating SARS-CoV-2 variants, including omicron variants and those carrying 3CL[SUP]pro[/SUP] mutations, which emerging novel SARS-CoV-2 variants could carry.
Keywords: 3C-like protease (3CL(pro)); Ensitrelvir; SARS-CoV-2.
. 2023 Jan 14;645:132-136.
doi: 10.1016/j.bbrc.2023.01.040. Online ahead of print.
Ensitrelvir is effective against SARS-CoV-2 3CL protease mutants circulating globally
Sho Kawashima[SUP] 1 [/SUP], Yuki Matsui[SUP] 2 [/SUP], Takumi Adachi[SUP] 2 [/SUP], Yuji Morikawa[SUP] 2 [/SUP], Kae Inoue[SUP] 3 [/SUP], Shiori Takebayashi[SUP] 3 [/SUP], Haruaki Nobori[SUP] 1 [/SUP], Masatomo Rokushima[SUP] 2 [/SUP], Yuki Tachibana[SUP] 4 [/SUP], Teruhisa Kato[SUP] 5 [/SUP]
Affiliations
- PMID: 36689809
- DOI: 10.1016/j.bbrc.2023.01.040
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a public health concern worldwide. Ensitrelvir (S-217622) has been evaluated as an antiviral treatment for COVID-19, targeting SARS-CoV-2 3C-like protease (3CL[SUP]pro[/SUP]). Ensitrelvir has been reported to have comparable antiviral activity against some of the SARS-CoV-2 variants: alpha, beta, gamma, delta, and omicron (BA.1.18). In this paper, we describe that ensitrelvir is effective against newly emerging SARS-CoV-2 variants and globally prevalent 3CL[SUP]pro[/SUP] mutations. Ensitrelvir exhibited comparable antiviral activity against SARS-CoV-2 variants, including recently emerging ones: omicron (BA1.1, BA.2, BA.2.75, BA.4, BA.5, BQ.1.1, XBB.1, and XE), mu, lambda, and theta. Genetic surveillance of SARS-CoV-2 3CL[SUP]pro[/SUP], the target of ensitrelvir, was conducted using a public database and identified 11 major 3CL[SUP]pro[/SUP] mutations circulating globally (G15S, T21I, T24I, K88R, L89F, K90R, P108S, P132H, A193V, H246Y, and A255V). The 3CL[SUP]pro[/SUP] mutation from proline to histidine at amino acid position 132 was especially identified in the omicron variant, with prevalence of 99.69%. Enzyme kinetic assay revealed that these 3CL[SUP]pro[/SUP] mutants have enzymatic activity comparable to that of the wild type (WT). Next, we assessed the inhibitory effect of ensitrelvir against mutated 3CL[SUP]pro[/SUP], with it showing inhibitory effects similar to that against the WT. These in vitro data suggest that ensitrelvir will be effective against currently circulating SARS-CoV-2 variants, including omicron variants and those carrying 3CL[SUP]pro[/SUP] mutations, which emerging novel SARS-CoV-2 variants could carry.
Keywords: 3C-like protease (3CL(pro)); Ensitrelvir; SARS-CoV-2.