Vulnerability of The Male Reproductive System to SARS-CoV-2 Invasion: Potential Role for The Endoplasmic Reticulum Chaperone Grp78/HSPA5/BiP

Document Type : Review Article


1 Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

2 Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada

3 Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

4 Department of Physiology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Malaysia

5 School of Natural Medicine, Faculty of Community and Health Sciences, University of the Western Cape, Cape Town, South Africa

6 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt

7 Ajyal IVF Center, Ajyal Hospital, Sohag, Egypt

8 American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA


Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may adversely affect male reproductive tissues and male
fertility. This concern is elicited by the higher susceptibility and mortality rate of men to the SARS-CoV-2 mediated coronavirus disease-19 (COVID-19), compared to the women. SARS-CoV-2 enters host cells after binding to a functional receptor named angiotensin-converting enzyme-2 (ACE2) and then replicates in the host cells and gets released into the plasma. SARS-CoVs use the endoplasmic reticulum (ER) as a site for viral protein synthesis and processing, as well as glucose-regulated protein 78 (Grp78) is a key ER chaperone involved in protein folding by preventing newly synthesized proteins from aggregation.
Therefore, we analyzed Grp78 expression in various human organs, particularly male reproductive organs, using Broad
Institute Cancer Cell Line Encyclopedia (CCLE), the Genotype-Tissue Expression (GTEx), and Human Protein Atlas online
datasets. Grp78 is expressed in male reproductive tissues such as the testis, epididymis, prostate, and seminal vesicle. It can facilitate the coronavirus entry into the male reproductive tract, providing an opportunity for its replication. This link between the SARS-CoV-2 and the Grp78 protein could become a therapeutic target to mitigate its harmful effects on male fertility.


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