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

doi:10.1016/j.xcrm.2023.101127

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 journal › Article › peer-review

6 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 language	English
Article number	101127
Journal	Cell Reports Medicine
Volume	4
Issue number	8
DOIs	https://doi.org/10.1016/j.xcrm.2023.101127
State	Published - 15 Aug 2023
Externally published	Yes

Keywords

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

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10.1016/j.xcrm.2023.101127

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Narayan, R., Sharma, M., Yadav, R., Biji, A., Khatun, O., Kaur, S., Kanojia, A., Joy, C. M., Rajmani, R., Sharma, P. R., Jeyasankar, S., Rani, P., Shandil, R. K., Narayanan, S., Rao, D. C., Satchidanandam, V., Das, S., Agarwal, R., & Tripathi, S. (2023). Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo. Cell Reports Medicine, 4(8), Article 101127. https://doi.org/10.1016/j.xcrm.2023.101127

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

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.",

keywords = "SARS-CoV-2, antiviral, influenza, membrane fusion, picolinic acid, pre-clinical animal models, viral entry",

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

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year = "2023",

month = aug,

day = "15",

doi = "10.1016/j.xcrm.2023.101127",

language = "English",

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Narayan, R, Sharma, M, Yadav, R, Biji, A, Khatun, O, Kaur, S, Kanojia, A, Joy, CM, Rajmani, R, Sharma, PR, Jeyasankar, S, Rani, P, Shandil, RK, Narayanan, S, Rao, DC, Satchidanandam, V, Das, S, Agarwal, R & Tripathi, S 2023, 'Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo', Cell Reports Medicine, vol. 4, no. 8, 101127. https://doi.org/10.1016/j.xcrm.2023.101127

TY - JOUR

T1 - Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo

AU - Narayan, Rohan

AU - Sharma, Mansi

AU - Yadav, Rajesh

AU - Biji, Abhijith

AU - Khatun, Oyahida

AU - Kaur, Sumandeep

AU - Kanojia, Aditi

AU - Joy, Christy Margrat

AU - Rajmani, Raju

AU - Sharma, Pallavi Raj

AU - Jeyasankar, Sharumathi

AU - Rani, Priya

AU - Shandil, Radha Krishan

AU - Narayanan, Shridhar

AU - Rao, Durga Chilakalapudi

AU - Satchidanandam, Vijaya

AU - Das, Saumitra

AU - Agarwal, Rachit

AU - Tripathi, Shashank

PY - 2023/8/15

Y1 - 2023/8/15

N2 - 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.

AB - 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.

KW - SARS-CoV-2

KW - antiviral

KW - influenza

KW - membrane fusion

KW - picolinic acid

KW - pre-clinical animal models

KW - viral entry

UR - http://www.scopus.com/inward/record.url?scp=85167777333&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2023.101127

DO - 10.1016/j.xcrm.2023.101127

M3 - Article

C2 - 37463584

AN - SCOPUS:85167777333

SN - 2666-3791

VL - 4

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 8

M1 - 101127

ER -

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

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Keywords

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