Assessment of cytotoxicity and antiviral activity against SARS-CoV-2 of the mixture of lactoferrin, artemisinin, and azithromycin in vitro

Lactoferrin, artemisinin, and azithromycin exhibit a broad spectrum of antiviral, immunomodulatory, and anti-inflammatory effects. The experiments show that these drugs partially inhibit the infection caused by SARS-CoV-2 in vitro. This allows us to conclude that the effects on the entry of virions into cells mediated by each of these substances taken separately are insufficient for complete inhibition of the SARS-CoV-2 infection. The study was aimed to perform in vitro assessment of cytotoxicity and antiviral activity against the laboratory SARS-CoV-2 strain of the mixture of active ingredients: lactoferrin, artemisinin, and azithromycin. We used the Vero CCL81 (ATСС) cell line and the Dubrovka laboratory strain of SARS-CoV-2 (GenBank ID: MW161041.1), isolated in the Vero CCL81 cell culture from the nasopharyngeal swab of patient with СOVID-19. Cytotoxic effects and antiviral activity against SARS-CoV-2 of the drug mixture were assessed based on the cytopathic effects using the MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay. Hydroxychloroquine was used as a reference drug. It has been shown that at high (MOI 100) and low (MOI 20) multiplicity of infection used in the Vero CCL 81 cell culture, the mixture of artemisinin, lactoferrin and azithromycin has a significant effect on the SARS-CoV-2 reproduction, and IC50 (half maximal inhibitory concentration) is estimated as the 1 : 2 dilution in both cases. The findings make it possible to conclude that the studied mixture is low toxic and shows significant antiviral effects in vitro.