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Linoleic acid binds to SARS-CoV-2 RdRp and represses replication of seasonal human coronavirus OC43
Anna Goc1, Waldemar Sumera2, Matthias Rath2
1Dr. Rath Research Institute, 5941 Optical Ct., San Jose, CA, 95138, USA. a.goc@drrath.com.
Abstract:
Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficacy. However, little is yet known about their effect on replication of human coronaviruses. To shed light on this subject, we first screened 15 fatty acids, three lipid-soluble vitamins, and cholesterol, on SARS-CoV-2 RdRp, and identified the four fatty acids with the highest RdRp inhibitory potential. Among them, linoleic acid was found to have the greatest interaction with SARS-CoV-2 RdRp, with its direct binding to the cavity formed by the RNA double helix and protein. Linoleic acid forms hydrophobic interactions with multiple residues, and at the same time forms electrostatic interactions including the hydrogen bond with Lys593 and Asp865. In line with these results, a dose-dependent inhibition of HCoV-OC43 replication in vitro was observed, additionally strengthened by data from in vivo study, which also confirmed anti-inflammatory potential of linoleic acid. Based on these results, we concluded that our study provides a new understanding of the antiviral properties of fatty acids against human coronaviruses including the SARS-CoV-2 strain. Particularly, they lays down a new prospect for linoleic acid's RdRp-inhibitory activity, as a candidate for further studies, which are warranted to corroborate the results presented here.
Insights
Linoleic acid shows significant potential in inhibiting human coronavirus replication by interacting with the SARS-CoV-2 RNA-dependent RNA polymerase. This fatty acid also exhibits anti-inflammatory properties, suggesting its therapeutic value.
Area of Science:
- Biochemistry
- Virology
- Pharmacology
Background:
- Fatty acids are known for broad antiviral activity.
- The effect of fatty acids on human coronavirus replication remains largely unexplored.
- Human coronaviruses pose a significant public health threat.
Purpose of the Study:
- To investigate the antiviral properties of fatty acids against human coronaviruses.
- To identify specific fatty acids that inhibit SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).
- To elucidate the mechanism of action for effective fatty acids.
Main Methods:
- Screening of 15 fatty acids, 3 lipid-soluble vitamins, and cholesterol for SARS-CoV-2 RdRp inhibition.
- Molecular interaction analysis of linoleic acid with SARS-CoV-2 RdRp.
- In vitro assessment of HCoV-OC43 replication inhibition.
- In vivo study to confirm antiviral and anti-inflammatory effects.
Main Results:
- Four fatty acids demonstrated significant RdRp inhibitory potential.
- Linoleic acid exhibited the strongest interaction with SARS-CoV-2 RdRp, binding within a specific cavity.
- Linoleic acid formed hydrophobic and electrostatic interactions with viral RdRp residues.
- Dose-dependent inhibition of HCoV-OC43 replication was observed in vitro.
- In vivo studies confirmed the antiviral and anti-inflammatory effects of linoleic acid.
Conclusions:
- Fatty acids possess antiviral properties against human coronaviruses, including SARS-CoV-2.
- Linoleic acid demonstrates promising RdRp-inhibitory activity and warrants further investigation as a potential antiviral therapeutic.
- The study provides new insights into the mechanism of fatty acid antiviral action.
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