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.

Hemoperfusion is a method of blood filtering to remove toxins and inflammatory factors. Cytokine storms and high levels of inflammatory factors play a role in the pathogenesis of coronavirus disease 2019 (COVID-19). The present study aims to evaluate the effect of hemoperfusion on the clinical and laboratory findings and outcomes of patients with severe COVID-19. Forty-eight patients with severe COVID-19 and a positive PCR test who were admitted to the intensive care unit (ICU) participated in the study. All patients were treated by routine treatment protocol for COVID-19. Hemoperfusion was performed for 24 patients in addition to treatment with conventional antiviral therapies. The other 24 patients made up the control group. Demographic data, laboratory findings, and patient outcomes before and after treatment were retrospectively collected and analyzed. There was no significant difference in mortality or length of hospital stays between the control group and the hemoperfusion group. The breathing rate (P-value=0.001) and heart beat rate (P-value=0.028) of patients decreased after hemoperfusion. The hemoperfusion resulted in a significant increase in the SpO2 levels and a significant decrease in the CRP of patients compared to the conventional treatment (P-value=0.009). Hemoperfusion can improve respiratory distress. It can reduce the CRP in patients with severe COVID-19 but has no effect on mortality.

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Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the poorest outcomes, and is associated with a high risk of relapse and metastasis. The treatment choices for this malignancy have been confined to conventional chemotherapeutic agents, due to a lack of expression of the canonical molecular targets. Immunotherapy has been recently changing the treatment paradigm for many types of tumors, and the approach of evoking active immune responses in the milieu of breast tumors through cancer vaccines has been introduced as one of the most novel immunotherapeutic approaches. Accordingly, a number of vaccines for the treatment or prevention of recurrence have been developed and are currently being studied in TNBC patients, while none have yet received any approvals. To elucidate the efficacy and safety of these vaccines, we performed a systematic review of the available literature on the topic. After searching the PubMed, Scopus, Web of Science, Embase, Cochrane CENTRAL, and Google Scholar databases, a total of 5701 results were obtained, from which 42 clinical studies were eventually included based on the predefined criteria. The overall quality of the included studies was acceptable. However, due to a lack of reporting outcomes of survival or progression in some studies (which were presented as conference abstracts) as well as the heterogeneity of the reported outcomes and study designs, we were not able to carry out a meta-analysis. A total of 32 different vaccines have so far been evaluated in TNBC patients, with the majority belonging to the peptide-based vaccine type. The other vaccines were in the cell or nucleic acid (RNA/DNA)-based categories. Most vaccines proved to be safe with low-grade, local adverse events and could efficiently evoke cellular immune responses; however, most trials were not able to demonstrate significant improvements in clinical indices of efficacy. This is in part due to the limited number of randomized studies, as well as the limited TNBC population of each trial. However, due to the encouraging results of the currently published trials, we anticipate that this strategy could show its potential through larger, phase III randomized studies in the near future.