Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo

Rohan Narayan, Mansi Sharma, Rajesh Yadav, Abhijith Biji, Oyahida Khatun, Sumandeep Kaur, Aditi Kanojia, Christy Margrat Joy, Raju Rajmani, Pallavi Raj Sharma, Sharumathi Jeyasankar, Priya Rani, Radha Krishan Shandil, Shridhar Narayanan, Durga Chilakalapudi Rao, Vijaya Satchidanandam, Saumitra Das, Rachit Agarwal, Shashank Tripathi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Article number101127
JournalCell Reports Medicine
Volume4
Issue number8
DOIs
StatePublished - 15 Aug 2023
Externally publishedYes

Keywords

  • SARS-CoV-2
  • antiviral
  • influenza
  • membrane fusion
  • picolinic acid
  • pre-clinical animal models
  • viral entry

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