tetano
Editor, Senior Moderator
Cell Rep Med
. 2023 Jul 13;101127.
doi: 10.1016/j.xcrm.2023.101127. Online ahead of print. Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo
Rohan Narayan[SUP] 1 [/SUP], Mansi Sharma[SUP] 1 [/SUP], Rajesh Yadav[SUP] 2 [/SUP], Abhijith Biji[SUP] 1 [/SUP], Oyahida Khatun[SUP] 1 [/SUP], Sumandeep Kaur[SUP] 1 [/SUP], Aditi Kanojia[SUP] 1 [/SUP], Christy Margrat Joy[SUP] 1 [/SUP], Raju Rajmani[SUP] 3 [/SUP], Pallavi Raj Sharma[SUP] 4 [/SUP], Sharumathi Jeyasankar[SUP] 4 [/SUP], Priya Rani[SUP] 5 [/SUP], Radha Krishan Shandil[SUP] 6 [/SUP], Shridhar Narayanan[SUP] 6 [/SUP], Durga Chilakalapudi Rao[SUP] 7 [/SUP], Vijaya Satchidanandam[SUP] 5 [/SUP], Saumitra Das[SUP] 5 [/SUP], Rachit Agarwal[SUP] 4 [/SUP], Shashank Tripathi[SUP] 8 [/SUP]
Affiliations
The COVID-19 pandemic highlights an urgent need for effective antivirals. Targeting host processes co-opted by viruses is an attractive antiviral strategy with a high resistance barrier. Picolinic acid (PA) is a tryptophan metabolite endogenously produced in mammals. Here, we report the broad-spectrum antiviral activity of PA against enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), flaviviruses, herpes simplex virus, and parainfluenza virus. Mechanistic studies reveal that PA inhibits enveloped virus entry by compromising viral membrane integrity, inhibiting virus-cellular membrane fusion, and interfering with cellular endocytosis. More importantly, in pre-clinical animal models, PA exhibits promising antiviral efficacy against SARS-CoV-2 and IAV. Overall, our data establish PA as a broad-spectrum antiviral with promising pre-clinical efficacy against pandemic viruses SARS-CoV-2 and IAV.
Keywords: SARS-CoV-2; antiviral; influenza; membrane fusion; picolinic acid; pre-clinical animal models; viral entry.
. 2023 Jul 13;101127.
doi: 10.1016/j.xcrm.2023.101127. Online ahead of print. Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo
Rohan Narayan[SUP] 1 [/SUP], Mansi Sharma[SUP] 1 [/SUP], Rajesh Yadav[SUP] 2 [/SUP], Abhijith Biji[SUP] 1 [/SUP], Oyahida Khatun[SUP] 1 [/SUP], Sumandeep Kaur[SUP] 1 [/SUP], Aditi Kanojia[SUP] 1 [/SUP], Christy Margrat Joy[SUP] 1 [/SUP], Raju Rajmani[SUP] 3 [/SUP], Pallavi Raj Sharma[SUP] 4 [/SUP], Sharumathi Jeyasankar[SUP] 4 [/SUP], Priya Rani[SUP] 5 [/SUP], Radha Krishan Shandil[SUP] 6 [/SUP], Shridhar Narayanan[SUP] 6 [/SUP], Durga Chilakalapudi Rao[SUP] 7 [/SUP], Vijaya Satchidanandam[SUP] 5 [/SUP], Saumitra Das[SUP] 5 [/SUP], Rachit Agarwal[SUP] 4 [/SUP], Shashank Tripathi[SUP] 8 [/SUP]
Affiliations
- PMID: 37463584
- DOI: 10.1016/j.xcrm.2023.101127
The COVID-19 pandemic highlights an urgent need for effective antivirals. Targeting host processes co-opted by viruses is an attractive antiviral strategy with a high resistance barrier. Picolinic acid (PA) is a tryptophan metabolite endogenously produced in mammals. Here, we report the broad-spectrum antiviral activity of PA against enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), flaviviruses, herpes simplex virus, and parainfluenza virus. Mechanistic studies reveal that PA inhibits enveloped virus entry by compromising viral membrane integrity, inhibiting virus-cellular membrane fusion, and interfering with cellular endocytosis. More importantly, in pre-clinical animal models, PA exhibits promising antiviral efficacy against SARS-CoV-2 and IAV. Overall, our data establish PA as a broad-spectrum antiviral with promising pre-clinical efficacy against pandemic viruses SARS-CoV-2 and IAV.
Keywords: SARS-CoV-2; antiviral; influenza; membrane fusion; picolinic acid; pre-clinical animal models; viral entry.