Progress on SARS-CoV-2 cell entry inhibitors / 中国药理学通报

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.

HIV small-molecule entry inhibitors targeting gp120, CD4 and CXCR4:research advances / 国际药学研究杂志

AIDS is an infectious disease caused by human immunodeficiency virus(HIV)and has done great harm to human beings. The envelope glycoprotein surface subunit gp120 and its receptor CD4 and coreceptor CXCR4 play important roles in HIV-1 en?try. The Phe43 pocket and Arg59 of gp120 are two important regions that interact with CD4. Recently,HIV small-molecule entry inhib?itors have become a hot topic in anti-HIV drug research,which are able to inhibit the virus before the cells are infected. The Phe43 pocket is an attractive target and the study of Phe43 pocket-targeting small-molecule entry inhibitors is underway,including BMS-378806,BHS-488043 and its analogs,and NBD-556 and its analogs. Besides,CXCR4 antagonist is another important approach.

Defeating enemy outside the border-development of viral entry inhibitors / 复旦学报（医学版）

About 25 years ago,we had pioneered the research fields of developing human immunodeficiency virus (HIV) fusion/entry inhibitors and anti-HIV peptide drugs.Over the past six years,we have gained some promising results in research and development of the HIV,Middle East respiratory syndrome coronavirus (MERS-COV),the Ebola virus (EBOV),and the Zika virus (ZIKV) entry inhibitors.This article provides an overview of the research progress of viral entry inhibitors against the related highly pathogenic viruses.

HIV small-molecule entry inhibitors targeting gp120, CD4 and CXCR4: Research advances / 国际药学研究杂志

AIDS is an infectious disease caused by human immunodeficiency virus (HIV) and has done great harm to human beings. The envelope glycoprotein surface subunit gp120 and its receptor CD4 and coreceptor CXCR4 play important roles in HIV-1 entry. The Phe43 pocket and Arg59 of gp120 are two important regions that interact with CD4. Recently, HIV small-molecule entry inhibitors have become a hot topic in anti-HIV drug research, which are able to inhibit the virus before the cells are infected. The Phe43 pocket is an attractive target and the study of Phe43 pocket-targeting small-molecule entry inhibitors is underway, including BMS-378806, BHS-488043 and its analogs, and NBD-556 and its analogs. Besides, CXCR4 antagonist is another important approach.

The anti-HIV-1 entrance activity and mechanism of action of myriceric acid B from Rhoiptelea chiliantha Diels et Hand-Mazz / 中国药理学通报

Aim To investigate the HIV-1 entry inhibitory activities of myriceric acid B and C isolated from Rhoiptelea chiliantha Diels et Hand-Mazz and their mechanism of action.Method The plasmids encoding envelope proteins of HIV-1 (pHXB2) and VSV (pVSV-G) were cotransfected 293T cells with pNL4-3.Luc.R-E- to produce HIV-1 Env pseudovirus and VSV-G pseudovirus,respectively,which were used for testing the antiviral activities of these compounds.ELISA and molecular docking were used to study the mechanism of action of the active compounds.Results Myriceric acid B could significantly inhibit the infection of HIV-1 Env pseudovirus with an IC_(50) of(8.3±0.2)mg·L~(-1).The carbonoxyl group at C-28 position and the hydroxyl group at the C-3 position of myriceric acid B are important for its anti-HIV-1 activity.Like other HIV-1 entry inhibitors targeting gp41 (eg,ADS-J1 and NB-64), myriceric acid B could also block the gp41 six-helix bundle formation.Molecular docking analysis suggests that myriceric acid B may bind to the hydrophobic cavity of the gp41 N-trimeric coiled coil.Conclusion Myriceric acid B is a potent HIV-1 entry inhibitor targeting gp41 and can serve as a lead compound for developing novel anti-HIV-1 drug.

Research progress on the structure of HIV envelope glycoprotein and related HIV entry inhibitors / 中国药理学通报

HIV-1 envelope glycoprotein gp120 and gp41 are considered as two important parts in viral entry.In the process of virus entry,CD4 first binds to gp120 and causes the conformation of gp120 to change.Furthermore the conformation of gp41 has also been changed.Many peptides,macromolecular compounds and small molecule compounds which bind to gp120 or gp41 can deter the progress of virus entry.These compounds can play an important role in halting the spread of HIV-1 in this way.The structure and interaction of gp120 and gp41 are reviewed here,as well as the anti-HIV agents blocking the HIV entry by targeting the HIV-1 envelope glycoprotein.

Advancement in developing a new class of anti-AIDS drugs: HIV entry inhibitors / 中国药理学通报

Process of HIV fusion with target cells, mediated by the HIV envelope glycoprotein surface subunit gp120 and the transmembrane subunit gp41, is an important step for drug intervention. The membrane fusion events leading to HIV entry into the target cell are initiated by the binding of gp120 to CD4 and subsequently to a co-receptor, CXCR4 or CCR5. Consequently, gp41 undergoes conformational changes, resulting in the fusion between the viral and cellular membranes or between the infected and uninfected cells. Therefore, gp120 and gp41 on the virions and CD4 and coreceptors on the target cells may serve as targets for development of a new class of anti-HIV drugs, HIV entry inhibitors, with a mechanism of action different from those mediated by reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs), the two classes of antiretroviral drugs approved by FDA for clinical application. The successful development of a peptidic anti-HIV drug T-20, which is targeted to the HIV gp41, implies that HIV entry inhibitors are milestone in the current anti-HIV therapy. Application of the HIV entry inhibitors alone or in combination with the RTIs and PIs will increase the efficacy and reduce the toxicity of these anti-HIV drugs and will save lives of AIDS patients who fail to response to the current antiretroviral drugs. The advancement in the study and development of the HIV entry inhibitors was reviewed here in detail