Targeting host cell proteases as a potential treatment strategy to limit the spread of SARS‐CoV‐2 in the respiratory tract

Abstract

As the death toll of Coronavirus disease 19 (COVID‐19) continues to rise worldwide, it is imperative to explore novel molecular mechanisms for targeting SARS‐CoV‐2. Rather than looking for drugs that directly interact with key viral proteins inhibiting its replication, an alternative and possibly add‐on approach is to dismantle the host cell machinery that enables the virus to infect the host cell and spread from one cell to another. Excellent examples of such machinery are host cell proteases whose role in viral pathogenesis has been demonstrated in numerous coronaviruses. In this review, we propose two therapeutic modalities to tackle SARS‐CoV‐2 infections; the first is to transcriptionally modulate the expression of cellular proteases and their endogenous inhibitors and the second is to directly inhibit their enzymatic activity. We present a nonexhaustive collection of clinically investigated drugs that act by one of these mechanisms and thus represent promising candidates for preclinical in vitro testing and hopefully clinical testing in COVID‐19 patients.

Psychoanalysis of the doctrine of acute pneumonia

“…The dominant ideas about circulatory disorders in patients with AP are in contradiction with the fundamental research on the role of the lungs in the vital activity of this system (Figure 1). The infl uence of the focus of infl ammation on this function of the organ is replaced by the concept of the dependence of these disorders on the action of the infectious factor [31,32,[36][37][38][39][40].…”

“…Now comes the viral season in the etiology of AP, but the search for optimal treatment options continues on the basis of previous conceptual views on this disease. The purpose of such studies is to study the features of COVID-19 pneumonia based on the properties of the coronavirus and the expected consequences of its aggression [31,32,[36][37][38][39][40]. At the same time, infl ammation of the lung tissue, which is a distinctive characteristic of the disease and determines the originality and severity of its course, is considered as a sign, and not its basis.…”

Look at the COVID-19 Pandemic with an Open Mind

“…In fact, we are talking about the treatment of viral pneumonia as the main threat of coronavirus infection, but the proposals for a new strategy to solve this problem are only a continuation of the previous concept of the AP. In fact, tactical solutions are proposed without revising the disease strategy, and the pathogen continues to be considered as the main factor not only in the development, but also in the dynamics of the process [8,[26][27][28][29][30][31].…”

“…Current trends in the study of the COVID-19 problem are focused on the cellular, molecular, and even genetic level of research, which involves the study of the mechanisms of coronavirus aggression and ways to eliminate them [1,26,27,[31][32][33][34]. Of course, the results of such studies are very necessary in order to prevent the intracellular penetration of viruses and reduce the frequency of diseases, but today the main question that requires the fastest possible answer is to effectively help the endless stream of already ill patients who are waiting for him now, today, and not tomorrow.…”

Psychoanalysis of Ideas about Acute Pneumonia

“…The dominant ideas about circulatory disorders in patients with AP are in contradiction with the fundamental research on the role of the lungs in the vital activity of this system (see figure). The influence of the focus of inflammation on this function of the organ is replaced by the concept of the dependence of these disorders on the action of the infectious factor (31,32,(36)(37)(38)(39)(40). Such concepts suggest the wrong direction of therapeutic efforts, which may not bring the expected effect.…”