Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses

Abstract

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens.

SARS-CoV-2 Omicron variant is highly sensitive to molnupiravir, nirmatrelvir, and the combination

“…S3g–i ). Drug combination has recently been proposed as a first line of defense against coronaviruses, 13 and we expect that the combination of molnupiravir and nirmatrelvir is essential to enhance antiviral potency, limit toxicity, and avoid drug resistance in COVID-19 patients. Effective antiviral treatment, especially the rapid reduction of viral load, is expected to improve patient outcome but also limit virus transmission.…”

Broad-spectrum mono- and combinational drug therapies for global viral pandemic preparedness

“…For example, mutations in HCV proteins confer resistance to NS3-4A, NS5A and NS5B inhibitors [20]. To mitigate the development of antiviral drug resistance, antivirals are combined [21]. Additive, multiplicative, and synergistic drug combinations are more effective than monotherapies, allowing for successful treatments at lower dosage and reduction of harmful side effects.…”

“…In particular, we will test selected drug cocktails in cell cultures against several life-threatening viruses and calculate synergy indexes to precisely distinguish synergistic from additive and antagonistic BCCs. Mathematical models that consider in vitro drug potency, pharmacokinetic and pharmacodynamic properties, and viral kinetics will further support prioritization of BCCs for in vivo studies [21]. We will than evaluate toxicity and efficacy, the immunological properties, and routes of administrations of BCCs using harmonized methods.…”

Broad-Spectrum Antivirals and Antiviral Drug Combinations

“…BSAs inhibit the replication of multiple viruses from the same or different viral families. To mitigate the development of antiviral drug resistance and increase their efficacy, antivirals are combined into BSA-containing drug cocktails (BCCs) [4][5][6]. Synergistic BCCs have lower concentrations of antivirals, which reduces their toxicity and side effects.…”

“…Many more BSAs and BCCs are awaiting discovery and development. However, new methods are needed to identify and prioritize the development of a few of the thousands of potential pan-and cross-virus family therapeutic [5,13]. Such methods can assist the global health community by providing new options to fight ongoing and recurrent viral outbreaks.…”