Brilacidin, a COVID‐19 drug candidate, demonstrates broad‐spectrum antiviral activity against human coronaviruses OC43, 229E, and NL63 through targeting both the virus and the host cell
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Abstract
Brilacidin, a mimetic of host defense peptides (HDPs), is currently in Phase 2 clinical trial as an antibiotic drug candidate. A recent study reported that brilacidin has antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by inactivating the virus. In this study, we discovered an additional mechanism of action of brilacidin by targeting heparan sulfate proteoglycans (HSPGs) on the host cell surface. Brilacidin, but not acetyl brilacidin, inhibits the entry of SARS‐CoV‐2 pseudovirus into multiple cell lines, and heparin, an HSPG mimetic, abolishes the inhibitory activity of brilacidin on SARS‐CoV‐2 pseudovirus cell entry. In addition, we found that brilacidin has broad‐spectrum antiviral activity against multiple human coronaviruses (HCoVs) including HCoV‐229E, HCoV‐OC43, and HCoV‐NL63. Mechanistic studies revealed that brilacidin has a dual antiviral mechanism of action including virucidal activity and binding to coronavirus attachment factor HSPGs on the host cell surface. Brilacidin partially loses its antiviral activity when heparin was included in the cell cultures, supporting the host‐targeting mechanism. Drug combination therapy showed that brilacidin has a strong synergistic effect with remdesivir against HCoV‐OC43 in cell culture. Taken together, this study provides appealing findings for the translational potential of brilacidin as a broad‐spectrum antiviral for coronaviruses including SARS‐CoV‐2.
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SciScore for 10.1101/2021.11.04.467344: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT01211470 Completed Initial Treatment for Acute Bacterial Skin … SciScore for 10.1101/2021.11.04.467344: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT01211470 Completed Initial Treatment for Acute Bacterial Skin Infections (ABSSS… NCT020388 Trial number did not resolve on clinicaltrials.gov. Is the number correct? NA NCT02324335 Completed Study of the Effects of Brilacidin Oral Rinse on Radiation-i… NCT04784897 Completed A Study to Evaluate the Efficacy and Safety of Brilacidin in… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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