Predicting In Vitro and In Vivo Anti-SARS-CoV-2 Activities of Antivirals by Intracellular Bioavailability and Biochemical Activity.
ACS Omega
; 7(49): 45023-45035, 2022 Dec 13.
Article
in English
| MEDLINE | ID: covidwho-2185526
ABSTRACT
Cellular drug response (concentration required for obtaining 50% of a maximum cellular effect, EC50) can be predicted by the intracellular bioavailability (F ic) and biochemical activity (half-maximal inhibitory concentration, IC50) of drugs. In an ideal model, the cellular negative log of EC50 (pEC50) equals the sum of log F ic and the negative log of IC50 (pIC50). Here, we measured F ic's of remdesivir, favipiravir, and hydroxychloroquine in various cells and calculated their anti-SARS-CoV-2 EC50's. The predicted EC50's are close to the observed EC50's in vitro. When the lung concentrations of antiviral drugs are higher than the predicted EC50's in alveolar type 2 cells, the antiviral drugs inhibit virus replication in vivo, and vice versa. Overall, our results indicate that both in vitro and in vivo antiviral activities of drugs can be predicted by their intracellular bioavailability and biochemical activity without using virus. This virus-free strategy can help medicinal chemists and pharmacologists to screen antivirals during early drug discovery, especially for researchers who are not able to work in the high-level biosafety lab.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Prognostic study
Language:
English
Journal:
ACS Omega
Year:
2022
Document Type:
Article
Affiliation country:
Acsomega.2c05376
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