Covid-19: anti-HIV drug could be effective against Sars-CoV-2 infection

ISS, March 3, 2022 - Cobicistat, a drug used in HIV / AIDS therapy, could have an effect against COVID-19. It is the result of a study, by now conducted only in vitro and in an animal model, published in the journal of the American Society of Microbiology, mBio, by an international group of researchers. According to the research, cobicistat inhibits the replication of SARS-CoV-2 with a different mechanism from those of the drugs currently used, i.e. by blocking the fusion of the virus to its target cells. Furthermore, the drug can attenuate the progression of the disease in a hamster animal model (Mesocricetus auratus), by enhancing the effect of another drug previously tested against COVID, i.e. remdesivir.

Cobicistat was selected with a drug repositioning approach, as this compound is typically used as a booster to enhance the activity of HIV medications, increasing their blood levels. According to studies conducted during and immediately after the SARS-CoV epidemic (2003), also by Andrea Savarino (Italian Institute of Health, Rome), co-senior author of this research, the use of this class of boosters could potentially inhibit the protease of coronaviruses. However, attempts to use cobicistat at the onset of the SARS-CoV-2 epidemic had not yielded positive results. As the authors of the study explain, one of the main reasons is the dosage needed to obtain an inhibitory effect against the replication of the virus. "The study - explains Savarino - in fact shows that cobicistat effectively inhibits the replication of the SARS-CoV-2 virus at levels about four times higher than those administered in the initial clinical trials. Furthermore", he adds, "the research showed that the mechanism is different from that initially postulated on the basis of computer simulations. The drug does not inhibit the SARS-CoV-2 protease, but hinders the correct formation of the Spike protein, the same against which vaccines are targeted and which is used by the virus to into cells". As described in the article, this mechanism was confirmed by a series of experiments conducted with traditional and innovative techniques by three research groups, two at the University of Heidelberg, Germany, and at Yale University, USA. An important aspect found in the study is that high-dose cobicistat may increase the antiviral efficacy of remdesivir, not only in test tubes, but also in vivo in an animal model experiment conducted at the Freie Universität in Berlin. The importance of this observation also lies in the fact that remdesivir has so far shown partial clinical efficacy, as is evident from the conflicting results of large clinical trials. Therefore, an additional component capable of increasing the efficacy of remdesivir could represent an important step in the development of effective therapies against COVID.

"It is at this point very important to highlight the importance of combinational drug therapy rather than a monotherapeutic approach for viral infections" says Marina Lusic, assistant professor at the University of Heidelberg and co-senior author of the study. "This means", she adds, "that it is likely that in the future studies cobicistat will be combined with other anti-virals for treatment of SARS-CoV2".

"The most important aspect of our study" says Iart Luca Shytaj, visiting professor at the Federal University of Sao Paulo, Brazil, and lead author of the study "is the demonstration that a compound that supports the action of other drugs may also have an antiviral effect in vivo. This double effect could make it possible to test a wide range of pharmacological combinations to devise an optimal cocktail that can completely inhibit the replication of the virus ".

https://journals.asm.org/doi/10.1128/mbio.03705-21