Anti-viral treatment for SARS-CoV-2 infection: A race against time amidst the ongoing pandemic

Abstract

Remdesivir (GS-5734), a drug initially developed to treat hepatitis C and Ebola virus disease, was the first approved treatment for severe coronavirus disease 2019 (COVID-19). However, apart from remdesivir, there is a paucity of other specific anti-viral agents against SARS-CoV-2 infection. In 2017, researchers had documented the anti-coronavirus potential of remdesivir in animal models. At the same time, trials performed during two Ebola outbreaks in Africa showed that the drug was safe. Although vaccines against SARS-CoV-2 infection have emerged at an enormously high speed, equivalent results from efforts towards the development of anti-viral drugs, which could have played a truly life-saving role in the current stage of the pandemic, have been stagnating. In this review, we will focus on the current treatment options for COVID-19 which mainly consist of repurposed agents or treatments conferring passive immunity (convalescent plasma or monoclonal antibodies). Additionally, potential specific anti-viral therapies under development will be reviewed, such as the decoy miniprotein CTC-445.2d, protease inhibitors, mainly against the Main protein Mpro, nucleoside analogs, such as molnupiravir and compounds blocking the replication transcription complex proteins, such as zotatifin and plitidepsin. These anti-viral agents seem to be very promising but still require meticulous clinical trial testing in order to establish their efficacy and safety. The continuous emergence of viral variants may pose a real challenge to the scientific community towards that end. In this context, the advent of nanobodies together with the potential administration of a combination of anti-viral drugs could serve as useful tools in the armamentarium against COVID-19.

Keywords: Antiviral treatment; Baricitinib; COVID-19; Favipiravir; Molnupiravir; Monoclonal antibodies; Nanobodies; Plitidepsin; Protease inhibitors; Ribavirin; SARS-CoV-2; Zotatifin; boceprevir.

Figure 1

Life cycle of SARS-CoV-2 and potential anti-viral agents. SARS-CoV-2 infects host cells, reproduces itself and spreads depending on a variety of viral and host proteins. Key steps of the SARS-CoV-2 life cycle inhibited by current treatment options as well as promising antiviral agents that are currently being examined, represent attractive antiviral targets and are highlighted in red. These include ACE2 receptor inhibitors, ACE2 mimic compounds, fusion inhibitors, several protease inhibitors, RNA polymerase inhibitors, passive immunization with convalescent plasma, monoclonal antibodies or nanobodies. Furthermore, immunomodulators such as corticosteroids, a selective Janus kinase 1 and 2 inhibitor (baricitinib), and various agents targeting the interleukin-6 pathway are presented.