Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Recent studies have demonstrated the potential of natural killer(NK)cells in immunotherapy to treat multiple types of cancer.NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex.The discovery of the NK’s potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers.NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy.The effector role of these cells is reliant on the balance of inhibitory and activating signals.Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation.Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment;this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers.Accordingly,this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function,as well as their potential application in tumor immunotherapy.

Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs

The pandemic of novel coronavirus disease 2019(COVID-19)has rampaged the world,with more than 58.4 million confirmed cases and over 1.38 million deaths across the world by 23 November 2020.There is an urgent need to identify effective drugs and vaccines to fight against the virus.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)belongs to the family of coronaviruses consisting of four structural and 16 non-structural proteins(NSP).Three non-structural proteins,main protease(Mpro),papain-like protease(PLpro),and RNAdependent RNA polymerase(RdRp),are believed to have a crucial role in replication of the virus.We applied computational ligand-receptor binding modeling and performed comprehensive virtual screening on FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina,Glide,and rDock.Our computational studies identified six novel ligands as potential inhibitors against SARS-CoV-2,including antiemetics rolapitant and ondansetron for Mpro;labetalol and levomefolic acid for PLpro;and leucal and antifungal natamycin for RdRp.Molecular dynamics simulation confirmed the stability of the ligand-protein complexes.The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy(low inhibitory effect)with all three proteins—Mpro,PLpro,and RdRp.In summary,our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 inhibitors that may be considered for further clinical studies.