Enzymes in the time of COVID‐19: An overview about the effects in the human body, enzyme market, and perspectives for new drugs

Abstract

The rising pandemic caused by a coronavirus, resulted in a scientific quest to discover some effective treatments against its etiologic agent, the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). This research represented a significant scientific landmark and resulted in many medical advances. However, efforts to understand the viral mechanism of action and how the human body machinery is subverted during the infection are still ongoing. Herein, we contributed to this field with this compilation of the roles of both viral and human enzymes in the context of SARS‐CoV‐2 infection. In this sense, this overview reports that proteases are vital for the infection to take place: from SARS‐CoV‐2 perspective, the main protease (M pro ) and papain‐like protease (PL pro ) are highlighted; from the human body, angiotensin‐converting enzyme‐2, transmembrane serine protease‐2, and cathepsins (CatB/L) are pointed out. In addition, the influence of the virus on other enzymes is reported as the JAK/STAT pathway and the levels of lipase, enzymes from the cholesterol metabolism pathway, amylase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and glyceraldehyde 3‐phosphate dehydrogenase are also be disturbed in SARS‐CoV‐2 infection. Finally, this paper discusses the importance of detailed enzymatic studies for future treatments against SARS‐CoV‐2, and how some issues related to the syndrome treatment can create opportunities in the biotechnological market of enzymes and the development of new drugs.

Overview of Antiviral Drug Therapy for COVID-19: Where Do We Stand?

“…M protease (Mpro) and PL protease (PLpro), respectively known as nsp5 and nsp3, are essential enzymes in the virus replication cycle, representing a therapeutic target to prevent the success of the infection. They process the virus polyproteins into active proteins and differ from human proteases, promoting the lower toxicity of protease inhibitors [ 40 ]. Notably, nirmatrelvir (NM) is an oral protease inhibitor that is active by cleaving the 2 viral polyproteins; it is available in association with ritonavir ® , a strong cytochrome P450-3A4 inhibitor, that increases nirmatrelvir concentrations reducing the dose regimen and the side effects of the antiviral.…”