| dc.description.abstract | Today, combination antiviral therapy is one of the main methods of treatment of complex diseases, such as HIV, HCV and HBV. Antiviral drug combinations have advantages over monotherapies because of their greater efficacy, less toxicity, and their ability to combat coinfections or multiple viral agents at the same time. Moreover, monotherapy is more often associated with a high rate of viral drug resistance than treatment with multiple drugs.
In this thesis, we contribute to the development of combination antiviral therapy from two directions. First, we study novel antiviral combinations with synergistic effects against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis C virus (HCV), human immunodeficiency virus 1 (HIV-1) and echovirus 1 (EV1) in vitro. Secondly, we develop a database of antiviral drug combinations showing synergistic or additive effects against different types of human viruses.
As the result of the experimental work, we discovered that combinations of nelfinavir and convalescent serum, EIDD-2801, remdesivir, salinomycin, amodiaquine, homoharringtonine, or obatoclax showed synergistic activity against SARS-CoV-2 in human lung epithelial cells Calu-3, as well as a combination of amodiaquine plus salinomycin. We also detected that combinations of sofosbuvir plus brequinar or niclosamide are synergistic against HCV infection in Huh-7.5 cell culture. Also, we found that lamivudine-monensin and tenofovir-monensin combinations are synergistic against HIV-1 infection in human cervical TZM-bl cell line. In addition, we figured out that FDA-approved anti-cancer drug vemurafenib is an effective inhibitor of EV1.
Finally, we observed synergistic antiviral activity of vemurafenib with emetine, homoharringtonine, anisomycin, or cycloheximide against EV1 infection in human lung epithelial A549 cells. These results reveal that a synergistic effect is achieved when an antiviral agent targeting a virus is combined with another compound targeting a virus or a host.
As the result of the development of antiviral drug combination database, we included almost 1000 antiviral combinations and covered 612 unique drugs and 68 different viruses and presented a detailed statistics of development stages of each drug combination. This database is aimed to significantly help researchers and experienced physicians to reduce time in identifying new promising combinations based on already conducted studies | |
