tetano
Editor, Senior Moderator
Antiviral Res
. 2024 Nov 19:106039.
doi: 10.1016/j.antiviral.2024.106039. Online ahead of print. X-206 exhibits broad-spectrum anti-β-coronavirus activity, covering SARS-CoV-2 variants and drug-resistant isolates
Jiei Sasaki[SUP] 1 [/SUP], Akihiko Sato[SUP] 2 [/SUP], Michihito Sasaki[SUP] 3 [/SUP], Iori Okabe[SUP] 4 [/SUP], Kota Kodama[SUP] 5 [/SUP], Satoko Otsuguro[SUP] 6 [/SUP], Kosuke Yasuda[SUP] 7 [/SUP], Hirotatsu Kojima[SUP] 7 [/SUP], Yasuko Orba[SUP] 3 [/SUP], Hirofumi Sawa[SUP] 8 [/SUP], Katsumi Maenaka[SUP] 9 [/SUP], Yusuke Yanagi[SUP] 4 [/SUP], Takao Hashiguchi[SUP] 10 [/SUP]
Affiliations
Coronaviruses such as the Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2, causing MERS, SARS, and Coronavirus disease-19, respectively, are highly pathogenic to humans. Notably, several antiviral drugs against SARS-CoV-2, such as nirmatrelvir and remdesivir, have been approved. However, no approved vaccines or antiviral agents are available for other highly pathogenic β-coronaviruses. In this study, we identified two compounds, thapsigargin and X-206, that exhibit antiviral activities against SARS-CoV, MERS-CoV, and SARS-CoV-2. Notably, both compounds effectively inhibited the cell-to-cell fusion mediated by the Spike proteins of all three β-coronaviruses. X-206 exhibited antiviral activity against nirmatrelvir- and remdesivir-resistant SARS-CoV-2 isolates and SARS-CoV-2 variants, including Delta, BA.5, and XBB.1. Consequently, the mechanism of action of these compounds with anti-β-coronavirus activities may differ from that of the approved direct-acting drugs for SARS-CoV-2, thereby offering potential use as a cocktail with other antivirals, and serving as a chemical basis for developing therapeutic agents against β-coronaviruses in preparation for the next spillover and pandemic.
Keywords: COVID-19; MERS; SARS; antiviral compound; coronavirus.
. 2024 Nov 19:106039.
doi: 10.1016/j.antiviral.2024.106039. Online ahead of print. X-206 exhibits broad-spectrum anti-β-coronavirus activity, covering SARS-CoV-2 variants and drug-resistant isolates
Jiei Sasaki[SUP] 1 [/SUP], Akihiko Sato[SUP] 2 [/SUP], Michihito Sasaki[SUP] 3 [/SUP], Iori Okabe[SUP] 4 [/SUP], Kota Kodama[SUP] 5 [/SUP], Satoko Otsuguro[SUP] 6 [/SUP], Kosuke Yasuda[SUP] 7 [/SUP], Hirotatsu Kojima[SUP] 7 [/SUP], Yasuko Orba[SUP] 3 [/SUP], Hirofumi Sawa[SUP] 8 [/SUP], Katsumi Maenaka[SUP] 9 [/SUP], Yusuke Yanagi[SUP] 4 [/SUP], Takao Hashiguchi[SUP] 10 [/SUP]
Affiliations
- PMID: 39571911
- DOI: 10.1016/j.antiviral.2024.106039
Coronaviruses such as the Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2, causing MERS, SARS, and Coronavirus disease-19, respectively, are highly pathogenic to humans. Notably, several antiviral drugs against SARS-CoV-2, such as nirmatrelvir and remdesivir, have been approved. However, no approved vaccines or antiviral agents are available for other highly pathogenic β-coronaviruses. In this study, we identified two compounds, thapsigargin and X-206, that exhibit antiviral activities against SARS-CoV, MERS-CoV, and SARS-CoV-2. Notably, both compounds effectively inhibited the cell-to-cell fusion mediated by the Spike proteins of all three β-coronaviruses. X-206 exhibited antiviral activity against nirmatrelvir- and remdesivir-resistant SARS-CoV-2 isolates and SARS-CoV-2 variants, including Delta, BA.5, and XBB.1. Consequently, the mechanism of action of these compounds with anti-β-coronavirus activities may differ from that of the approved direct-acting drugs for SARS-CoV-2, thereby offering potential use as a cocktail with other antivirals, and serving as a chemical basis for developing therapeutic agents against β-coronaviruses in preparation for the next spillover and pandemic.
Keywords: COVID-19; MERS; SARS; antiviral compound; coronavirus.