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Objective:To investigate the expression of coronavirus disease 2019 (COVID-19) transmission-related receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human conjunctival tissue and its clinical significance.Methods:Fifty human conjunctival tissue specimens from 50 patients including 10 normal conjunctival tissues, 15 conjunctival papilloma tissues, 15 conjunctival nevus tissues and 10 conjunctival cyst tissues were collected from June 2019 to June 2020 at Xi'an People's Hospital.Ten corneal tissue samples from 10 patients with eyes removed due to trauma were collected as control.The distribution of ACE2 and TMPRSS2 in different corneal tissues was detected by the immunohistochemistry.The expression of ACE2 and TMPRSS2 was scored and compared.Reuse of the human samples and the research protocol was approved by an Ethics Committee of Xi'an People's Hospital (No.20190022). Written informed consent was obtained from each patient.Results:ACE2 and TMPRSS2 were both expressed in normal conjunctival epithelium, epithelial cells in conjunctiva papilloma and conjunctival nevus, and cells in conjunctiva cyst wall.ACE2 was mainly distributed in the superficial and intermediate cells of conjunctival epithelium, but not in the basal cells and goblet cells.TMPRSS2 was found in different layers of cells.The positive expression rates of ACE2 and TMPRSS2 in conjunctiva were both 100%.There was no significant difference in the expression intensity of ACE2 and TMPRSS2 among normal conjunctival tissue, conjunctival papilloma, conjunctival nevus and conjunctival cyst (all at P>0.05). Weakly expressed in corneal tissues, ACE2 and TMPRSS2 were more moderately and strongly expressed in conjunctival tissues.There were significant differences in the number of differently graded ACE2 and TMPRSS2 expression between normal conjunctival tissues, conjunctival papilloma, conjunctival nevus, conjunctival cyst and corneal tissues (ACE2: Z=-3.473, -4.183, -3.970, -3.873, all at P<0.01; TMPRSS2: Z=-4.119, -4.472, -4.443, -4.147, all at P<0.001). Conclusions:COVID-19 transmission-related receptors ACE2 and TMPRSS2 are expressed in human conjunctival tissue, which provides organological evidence for ocular surface transmission of COVID-19.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. The life cycle of SARS-CoV-2 is not clear, which is one of the reasons that only Remdesivir has been approved by FDA for treating COVID-19. Although some new vaccines have been a- vailable, the quick mutations of SARS-CoV-2 affect the effectiveness of vaccines, calling for further assessment of the persistence and safety of vaccines. Therefore, drug treatment and prevention are still effective ways to deal with the epidemic of SARS-CoV-2. The article briefly summarizes the molecular mechanism of SARS-CoV-2 entry based on the existing literature. This virus enters the cell through two main ways, that is, spike protein mediating membrane fusion with plasma membrane or endosome membrane. According to the targets, the article summarizes the reported inhibitors of SARS-CoV-2 entry into cells, aiming to provide a reference for following research and clinical application of anti-SARS-CoV-2 drugs.