Metformin Suppresses SARS-CoV-2 in Cell Culture
In Vitro study showing metformin inhibits SARS-CoV-2 in Caco2 cells. Metformin reduced viral titers by nearly 99%, and by about 90% when cells were treated prior to infection.
Parthasarathy et al., 19 Nov 2021, preprint, 3 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: bioRxiv preprint doi: https://doi.org/10.1101/2021.11.18.469078; this version posted November 19, 2021. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
available under aCC-BY-NC-ND 4.0 International license.
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Metformin Suppresses SARS-CoV-2 in Cell Culture
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Haripriya Parthasarathy1, Dixit Tandel1,2, and Krishnan H. Harshan1,2,€
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CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India 500007
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Academy for Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
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Correspondence: hkrishnan@ccmb.res.in
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Keywords
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SARS-CoV-2, COVID-19, anti-viral activity, Metformin, AMPK, Diabetes
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bioRxiv preprint doi: https://doi.org/10.1101/2021.11.18.469078; this version posted November 19, 2021. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
available under aCC-BY-NC-ND 4.0 International license.
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ABSTRACT
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People with diabetes are reported to have a higher risk of experiencing severe
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COVID-19 complications. Metformin, a first-line medication for type 2 diabetes, has
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antiviral properties. Some studies have indicated its prognostic potential in COVID-
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19. Here, we report that metformin significantly inhibits SARS-CoV-2 growth in cell
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culture models. SARS-CoV-2 infection of gut epithelial cell line, Caco2, resulted in
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higher phosphorylation of AMPK. Metformin reduced viral titers in the infected cells
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by nearly 99%, and by about 90% when cells were treated prior to infection.
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Metformin pre-treatment resulted in further phosphorylation of AMPK and caused a
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ten-fold reduction of viral titers indicating its potential in preventing naïve infections.
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Confirming the positive impact of AMPK activation, another AMPK activator AICAR
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substantially inhibited of viral titers and, AMPK inhibitor Compound C, augmented it
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considerably. Metformin treatment post-SARS-CoV-2 infection resulted in nearly
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hundred-fold reduction of viral titers, indicating that the antiviral potency of the drug
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is far higher in infected cells, while still being able to reduce fresh infection.
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Metformin displayed SARS-CoV-2 TCID50 and TCID90 at 3.5 and 8.9 mM,
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respectively. In conclusion, our study demonstrates that metformin is very effective in
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limiting the replication of SARS-CoV-2 in cell culture and thus possibly could offer
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double benefits to diabetic COVID-19 patients by lowering both blood glucose levels
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and viral load.
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