Targeted therapy strategies against SARS‐CoV‐2 cell entry mechanisms: A systematic review of in vitro and in vivo studies

Abstract

Due to the rapidly spreading of novel coronavirus disease (COVID‐19) worldwide, there is an urgent need to develop efficient vaccines and specific antiviral treatments. Pathways of the viral entry into cells are interesting subjects for targeted therapy of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The present study aims to provide a systematic evaluation of the most recent in vitro and in vivo investigations targeting SARS‐CoV‐2 cell entry. A systematic search was carried out in major medical sources, including MEDLINE (through PubMed), Web of Science, Scopus, and EMBASE. Combinations of the following search terms were used: SARS‐CoV‐2, in vitro, in vivo, preclinical, targeted therapy, and cell entry. A modified version of the Consolidated Standards of Reporting Trials and Systematic Review Centre for Laboratory Animal Experimentation assessment tools were applied for evaluating the risk of bias of in vitro and in vivo studies, respectively. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure. A total of 2,649 articles were identified through searching PubMed, Web of Science, Scopus, EMBASE, Google Scholar, and Biorxiv. Finally, 22 studies (one in vivo study and 21 in vitro studies) were included. The spike (S) glycoprotein of the SARS‐CoV‐2 was the main target of investigation in 19 studies. SARS‐CoV‐2 can enter into the host cells through endocytosis or independently. SARS‐CoV‐2 S protein utilizes angiotensin‐converting enzyme 2 or CD147 as its cell‐surface receptor to attach host cells. It consists of S1 and S2 subunits. The S1 subunit mediates viral attachment to the host cells, while the S2 subunit facilitates virus‐host membrane fusion. The cleavage of the S1–S2 protein, which is required for the conformational changes of the S2 subunit and processing of viral fusion, is regulated by the host proteases, including cathepsin L (during endocytosis) and type II membrane serine protease (independently). Targeted therapy strategies against SARS‐CoV‐2 cell entry mechanisms fall into four main categories: strategies targeting virus receptors on the host, strategies neutralizing SARS‐CoV‐2 spike protein, strategies targeting virus fusion to host cells, and strategies targeting endosomal and non‐endosomal dependent pathways of virus entry. Inhibition of the viral entry by targeting host or virus‐related components remains the most potent strategy to prevent and treat COVID‐19. Further high‐quality investigations are needed to assess the efficacy of the proposed targets and develop specific antivirals against SARS‐CoV‐2.

A systematic review of pregnant women with COVID-19 and their neonates

“…Since December 2019, COVID-19 has been a resident of the world. Early efforts ranged from the development of diagnostic assays [80][81][82][83] and specific therapeutics [84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102] to optimizing health monitoring [103,104]. Despite this effort, in addition to our knowledge and experience from the recent outbreaks [105], it mainly relied on non-pharmacological interventions to control the pandemic, e.g., quarantine and social isolation [106,107].…”

Microarray patches enable the development of skin-targeted vaccines against COVID-19

“…Specifically, the SARS-CoV-2 spike glycoprotein consists of S1 and S2 subunits that mediate viral entry to host cells. The S1 subunit binds to the angiotensin-converting enzyme 2 (ACE2) receptor of host cells through its receptor-binding domain (RBD), and the S2 subunit enables viral fusion with the target cell membrane [ [66] , [67] , [68] ]. The SARS-CoV-2 S glycoprotein is cleaved by host proteases at the boundary between the S1 and S2 subunits, separating S1 from S2.…”

Biosensing surfaces and therapeutic biomaterials for the central nervous system in COVID-19

“…The COVID-19's face is strange; on the one hand, it manifests itself as a multi-system disease characterized by autoinflammatory and autoimmune features [88,91,[158][159][160][161][162], and on the other hand, are people with immunodeficiency who also appear susceptible to infection and lethal complications [163][164][165][166]. Therefore, engineering biomaterials to selectively target the immune system components has the potential of inducing tolerance; for instance, toll-like receptors (TLRs) and APCs, which respectively mediate innate immune responses [167] and antigen-specific adaptive immune responses [166,[168][169][170][171]. Also, biomaterials offer tools to help cell-mediated immune responses against viral vaccines and gene delivery for vaccines against viral infections, such as HIV.…”