tetano
Editor, Senior Moderator
Nat Commun
. 2024 Aug 1;15(1):6503.
doi: 10.1038/s41467-024-50931-8. The small molecule inhibitor of SARS-CoV-2 3CLpro EDP-235 prevents viral replication and transmission in vivo
Michael H J Rhodin[SUP] 1 [/SUP], Archie C Reyes[SUP] 2 [/SUP], Anand Balakrishnan[SUP] 2 [/SUP], Nalini Bisht[SUP] 2 [/SUP], Nicole M Kelly[SUP] 2 [/SUP], Joyce Sweeney Gibbons[SUP] 2 [/SUP], Jonathan Lloyd[SUP] 2 [/SUP], Michael Vaine[SUP] 2 [/SUP], Tessa Cressey[SUP] 2 [/SUP], Miranda Crepeau[SUP] 2 [/SUP], Ruichao Shen[SUP] 2 [/SUP], Nathan Manalo[SUP] 2 [/SUP], Jonathan Castillo[SUP] 2 [/SUP], Rachel E Levene[SUP] 2 [/SUP], Daniel Leonard[SUP] 2 [/SUP], Tianzhu Zang[SUP] 2 [/SUP], Lijuan Jiang[SUP] 2 [/SUP], Kellye Daniels[SUP] 2 [/SUP], Robert M Cox[SUP] 3 [/SUP], Carolin M Lieber[SUP] 3 [/SUP], Josef D Wolf[SUP] 3 [/SUP], Richard K Plemper[SUP] 3 [/SUP], Sarah R Leist[SUP] 4 [/SUP], Trevor Scobey[SUP] 4 [/SUP], Ralph S Baric[SUP] 4 [/SUP], Guoqiang Wang[SUP] 2 [/SUP], Bryan Goodwin[SUP] 2 [/SUP], Yat Sun Or[SUP] 2 [/SUP]
Affiliations
The COVID-19 pandemic has led to the deaths of millions of people and severe global economic impacts. Small molecule therapeutics have played an important role in the fight against SARS-CoV-2, the virus responsible for COVID-19, but their efficacy has been limited in scope and availability, with many people unable to access their benefits, and better options are needed. EDP-235 is specifically designed to inhibit the SARS-CoV-2 3CLpro, with potent nanomolar activity against all SARS-CoV-2 variants to date, as well as clinically relevant human and zoonotic coronaviruses. EDP-235 maintains potency against variants bearing mutations associated with nirmatrelvir resistance. Additionally, EDP-235 demonstrates a ≥ 500-fold selectivity index against multiple host proteases. In a male Syrian hamster model of COVID-19, EDP-235 suppresses SARS-CoV-2 replication and viral-induced hamster lung pathology. In a female ferret model, EDP-235 inhibits production of SARS-CoV-2 infectious virus and RNA at multiple anatomical sites. Furthermore, SARS-CoV-2 contact transmission does not occur when naïve ferrets are co-housed with infected, EDP-235-treated ferrets. Collectively, these results demonstrate that EDP-235 is a broad-spectrum coronavirus inhibitor with efficacy in animal models of primary infection and transmission.
. 2024 Aug 1;15(1):6503.
doi: 10.1038/s41467-024-50931-8. The small molecule inhibitor of SARS-CoV-2 3CLpro EDP-235 prevents viral replication and transmission in vivo
Michael H J Rhodin[SUP] 1 [/SUP], Archie C Reyes[SUP] 2 [/SUP], Anand Balakrishnan[SUP] 2 [/SUP], Nalini Bisht[SUP] 2 [/SUP], Nicole M Kelly[SUP] 2 [/SUP], Joyce Sweeney Gibbons[SUP] 2 [/SUP], Jonathan Lloyd[SUP] 2 [/SUP], Michael Vaine[SUP] 2 [/SUP], Tessa Cressey[SUP] 2 [/SUP], Miranda Crepeau[SUP] 2 [/SUP], Ruichao Shen[SUP] 2 [/SUP], Nathan Manalo[SUP] 2 [/SUP], Jonathan Castillo[SUP] 2 [/SUP], Rachel E Levene[SUP] 2 [/SUP], Daniel Leonard[SUP] 2 [/SUP], Tianzhu Zang[SUP] 2 [/SUP], Lijuan Jiang[SUP] 2 [/SUP], Kellye Daniels[SUP] 2 [/SUP], Robert M Cox[SUP] 3 [/SUP], Carolin M Lieber[SUP] 3 [/SUP], Josef D Wolf[SUP] 3 [/SUP], Richard K Plemper[SUP] 3 [/SUP], Sarah R Leist[SUP] 4 [/SUP], Trevor Scobey[SUP] 4 [/SUP], Ralph S Baric[SUP] 4 [/SUP], Guoqiang Wang[SUP] 2 [/SUP], Bryan Goodwin[SUP] 2 [/SUP], Yat Sun Or[SUP] 2 [/SUP]
Affiliations
- PMID: 39090095
- DOI: 10.1038/s41467-024-50931-8
The COVID-19 pandemic has led to the deaths of millions of people and severe global economic impacts. Small molecule therapeutics have played an important role in the fight against SARS-CoV-2, the virus responsible for COVID-19, but their efficacy has been limited in scope and availability, with many people unable to access their benefits, and better options are needed. EDP-235 is specifically designed to inhibit the SARS-CoV-2 3CLpro, with potent nanomolar activity against all SARS-CoV-2 variants to date, as well as clinically relevant human and zoonotic coronaviruses. EDP-235 maintains potency against variants bearing mutations associated with nirmatrelvir resistance. Additionally, EDP-235 demonstrates a ≥ 500-fold selectivity index against multiple host proteases. In a male Syrian hamster model of COVID-19, EDP-235 suppresses SARS-CoV-2 replication and viral-induced hamster lung pathology. In a female ferret model, EDP-235 inhibits production of SARS-CoV-2 infectious virus and RNA at multiple anatomical sites. Furthermore, SARS-CoV-2 contact transmission does not occur when naïve ferrets are co-housed with infected, EDP-235-treated ferrets. Collectively, these results demonstrate that EDP-235 is a broad-spectrum coronavirus inhibitor with efficacy in animal models of primary infection and transmission.