A natural broad-spectrum inhibitor of enveloped virus entry, effective against SARS-CoV-2 and Influenza A Virus in preclinical animal models.

Narayan, R.; Sharma, M.; Yadav, R. T.; Biji, A.; Khatun, O.; Rajmani, R. S.; Sharma, P. R.; Jeyashankar, S.; Rani, P.; Rao, C. D.; Satchidanandam, V.; Das, S.; Agarwal, R.; Tripathi, S.

doi:10.1101/2022.02.16.480801

bioRxiv · 10.1101/2022.02.16.480801

A natural broad-spectrum inhibitor of enveloped virus entry, effective against SARS-CoV-2 and Influenza A Virus in preclinical animal models.

Narayan, R.·Sharma, M.·Yadav, R. T.·Biji, A.·Khatun, O.·Rajmani, R. S.·Sharma, P. R.·Jeyashankar, S.·Rani, P.·Rao, C. D.·Satchidanandam, V.·Das, S.·Agarwal, R.·Tripathi, S.

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Abstract

The COVID-19 pandemic has highlighted the need for novel antivirals for pandemic management and preparedness. Targeting host processes that are co-opted by viruses is an attractive strategy for developing antivirals with a high resistance barrier. Picolinic acid (PA) is a byproduct of tryptophan metabolism, endogenously produced in humans and other mammals. Here we report broad-spectrum antiviral effects of PA against enveloped viruses, including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), Influenza A virus (IAV), Flaviviruses, Herpes Simplex Virus, and Human Parainfluenza Virus. We further demonstrate using animal models that PA is effective against SARS-CoV-2 and IAV, especially as an oral prophylactic. The mode of action studies revealed that PA inhibits viral entry of enveloped viruses, primarily by interfering with viral-cellular membrane fusion, inhibiting virus-mediated syncytia formation, and dysregulating cellular endocytosis. Overall, our data establish PA as a broad-spectrum antiviral agent, with promising preclinical efficacy against pandemic viruses SARS-CoV-2 and IAV.

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Narayan, R., Sharma, M., Yadav, R. T., Biji, A., Khatun, O., Rajmani, R. S., Sharma, P. R., Jeyashankar, S., Rani, P., Rao, C. D., Satchidanandam, V., Das, S., Agarwal, R., Tripathi, S.. 2022-02-17. A natural broad-spectrum inhibitor of enveloped virus entry, effective against SARS-CoV-2 and Influenza A Virus in preclinical animal models.. https://doi.org/10.1101/2022.02.16.480801

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