Classification of the present pharmaceutical agents based on the possible effective mechanism on the COVID-19 infection

Abstract

Objectives There are several types of research on the COVID-19 disease which have been conducting. It seems that prevailing over the pandemic would be achieved only by mastering over the virus pathophysiology. We tried to categorize the massive amount of available information for useful interpretation. Evidence acquisition We searched databases with different keywords and search strategies that focus on virulence and pathophysiology of COVID-19. The present review has aimed to gather and categorize all implemented drugs based on the susceptible virulence mechanisms, and the pathophysiological events in the host cells, discussing and suggesting treatments. Results As a result, the COVID-19 lifecycle were categorized as following steps: “Host Cell Attachment” which is mainly conducted with ACE 2 receptors and TMPRSS2 from the host cell and Spike (S) protein, “Endocytosis Pathway” which is performed mainly by clathrin-mediated endocytosis, and “Viral Replication” which contains translation and replication of RNA viral genome. The virus pathogenicity is continued by “Inflammatory Reactions” which mainly caused moderate to severe COVID-19 disease. Besides, the possible effective therapeutics’ mechanism and the pharmaceutical agents that had at least one experience as a preclinical or clinical study on COVID-19 were clearly defined. Conclusion The treatment protocol would be occasional based on the stage of the infection and the patient situation. The cocktail of medicines, which could affect almost all mentioned stages of COVID-19 disease, might be vital for patients with severe phenomena. Graphical abstract The classification of the possible mechanism of medicines based on COVID-19 pathogenicity

Increased angiotensin-converting enzyme 2, sRAGE and immune activation, but lowered calcium and magnesium in COVID-19: association with chest CT abnormalities and lowered peripheral oxygen saturation

“…ACE2 is a common binding site for both SARS-CoV and SARS-CoV-2 (Zhu et al ., 2018, Hoffmann et al ., 2020). COVID-19 virus binds to ACE2 receptors in human cells through Spike proteins-S homotrimers with high affinity and leads mainly to endocytosis through the pathway of “ clathrin-mediated endocytosis (Amini Pouya et al ., 2020). After attachment, transmembrane serine protease 2 (TMPRSS2) and several lysosomal proteases cleave and activate the S-glycoprotein due to SARS-CoV-2 entry into the cell through endocytosis or direct membrane fusion with the host membrane (Vlachakis et al ., 2020).…”

Confronting the threat of SARS‑CoV‑2: Realities, challenges and therapeutic strategies (Review)

“…The first strain of SARS-CoV-2 was isolated from Wuhan, China on 24th January 2020 after the outbreak of COVID-19 (11). In similarity to other coronaviruses, SARS-CoV-2 consists of four structural proteins, namely the spike (S), envelope, membrane/ matrix (M) and nucleocapsid proteins (12). Non-structural proteins are produced after RNA genome expression in the host cell during formation of new virus particles (12).…”

“…In similarity to other coronaviruses, SARS-CoV-2 consists of four structural proteins, namely the spike (S), envelope, membrane/ matrix (M) and nucleocapsid proteins (12). Non-structural proteins are produced after RNA genome expression in the host cell during formation of new virus particles (12). On the surface of mature coronavirus, the S protein usually forms a crown-like trimer, an important morphological feature which differentiates coronaviruses from other viruses (11).…”

“…This leads to clathrin-mediated endocytosis (26,27), release of viral RNA and induction of viral replication. The viral genome codes for non-structural proteins containing polyproteins, nucleoproteins, RNA polymerase, 3-chymotrypsin-like protease, papain-like protease and helicase in the host cell in order to form new virus particles (12). The newly manufactured virus emerges via exocytosis where it binds again to ACE2, thus entering a vicious cycle of infecting other cells (12).…”

“…When SARS-CoV-2 targets host cells (13), the serine protease transmembrane protease serine 2 (TMPRSS2) is employed for S protein priming ( Fig. 1) (12,32,35). Notably, all ACE2-expressing pulmonary cells are also TMPRSS2-positive (35).…”