A painful lesson from the COVID-19 pandemic: the need for broad-spectrum, host-directed antivirals
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ournal of Translational Medicine Open Access
COMMENTARY
A painful lesson from the COVID‑19 pandemic: the need for broad‑spectrum, host‑directed antivirals Vipul C. Chitalia1,2 and Ali H. Munawar3*
Abstract While the COVID-19 pandemic has spurred intense research and collaborative discovery worldwide, the development of a safe, effective, and targeted antiviral from the ground up is time intensive. Therefore, most antiviral discovery efforts are focused on the re-purposing of clinical stage or approved drugs. While emerging data on drugs undergoing COVID-19 repurpose are intriguing, there is an undeniable need to develop broad-spectrum antivirals to prevent future viral pandemics of unknown origin. The ideal drug to curtail rapid viral spread would be a broad-acting agent with activity against a wide range of viruses. Such a drug would work by modulating host-proteins that are often shared by multiple virus families thereby enabling preemptive drug development and therefore rapid deployment at the onset of an outbreak. Targeting host-pathways and cellular proteins that are hijacked by viruses can potentially offer broad-spectrum targets for the development of future antiviral drugs. Such host-directed antivirals are also likely to offer a higher barrier to the development and selection of drug resistant mutations. Given that most approved antivirals do not target host-proteins, we reinforce the need for the development of such antivirals that can be used in pre- and post-exposure populations. Keywords: COVID-19, Broad-spectrum antivirals, Mechanism of action (MOA), Pandemics, Drug discovery and development, SARS-CoV-2, Host-directed antivirals, Antiviral drug design, Coronavirus (CoV), Drug design strategies, Prophylactic antiviral therapy Background The exponential global spread of SARS-CoV-2, the virus behind the COVID-19 pandemic, has stunned the world with a staggering socioeconomic and public health impact [1]. To date, this novel coronavirus has infected over 33 million people in 213 countries and resulted in over 1million deaths worldwide [2]. Despite SARS-CoV-2 being the seventh known coronavirus to infect humans, the therapeutic landscape has remained barren, creating an urgent demand for the development of effective therapeutics for COVID-19 patients. While effective *Correspondence: amunawar@bisect‑tx.com 3 Bisect Therapeutics, Inc., 45 Dan Road, Canton, MA, USA Full list of author information is available at the end of the article
COVID-19 management requires both antiviral and antiinflammatory treatment strategies, the need for a potent and safe antiviral for therapeutic and prophylactic use is undisputed. However, the expectations of developing safe and selective antiviral agents in a short time frame are impractical given that drug development from target discovery to approval takes 12 years on average [3]. Therefore, initial efforts have been focused on the repurposing of clinical stage or approved drugs. Even with therapeutic repurposing as a rapid strategy to redirect approved or clinical-
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