Article
Chemistry, Medicinal
Naoya Kitamura, Michael Dominic Sacco, Chunlong Ma, Yanmei Hu, Julia Alma Townsend, Xiangzhi Meng, Fushun Zhang, Xiujun Zhang, Mandy Ba, Tommy Szeto, Adis Kukuljac, Michael Thomas Marty, David Schultz, Sara Cherry, Yan Xiang, Yu Chen, Jun Wang
Summary: This study discovered 23R, one of the most potent and selective noncovalent SARS-CoV-2 MPpro inhibitors reported to date, and a novel binding pocket in MPpro that can be explored for inhibitor design.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Jun Wang, Yanmei Hu, Madeleine Zheng
Summary: Enterovirus A71 (EV-A71) is a significant human pathogen that particularly affects children. Existing vaccines for EV-A71 have limited protection and reduced efficacy against emerging strains. No approved antiviral for EV-A71 is currently available. Researchers have made progress in developing antivirals by targeting viral proteins and host factors, although some approaches have shown limited efficacy or side effects.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Virology
Yanmei Hu, Hyunil Jo, William F. DeGrado, Jun Wang
Summary: This study discovered the antiviral mechanism of Brilacidin, which inhibits the entry of multiple human coronaviruses by targeting HSPGs on the host cell surface. The study also found a strong synergistic effect of Brilacidin in combination with remdesivir against a specific coronavirus.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Pharmacology & Pharmacy
Chunlong Ma, Haozhou Tan, Juliana Choza, Yuyin Wang, Jun Wang
Summary: This study systematically characterizes the target specificity of Mpro inhibitors for COVID-19 and highlights the need for stringent hit validation in early-stage drug discovery.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Xu Zhou, Lingxiang Zhu, Cheryl Bondy, Jun Wang, Qianwen Luo, Yin Chen
Summary: Current options for preventing or treating influenza are limited. However, a new study has discovered that a small molecule inhibitor called AG1478 has potent antiviral activity against influenza. The inhibitor targets the Golgi-specific GBF1-ARF1 system, rather than the EGFR inhibitory activity or interferon. This discovery highlights the potential of targeting host factors like GBF1 for developing effective treatments against influenza.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Haozhou Tan, Yanmei Hu, Prakash Jadhav, Bin Tan, Jun Wang
Summary: This article summarizes the significant progress in structure-based design and high-throughput screening of SARS-CoV-2 papain-like protease (PLpro) inhibitors since the beginning of the pandemic. Encouraging achievements include the development of non-covalent and covalent inhibitors with favorable pharmacokinetic properties. The article also identifies knowledge gaps that need to be addressed to advance PLpro inhibitors to clinical application.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Haozhou Tan, Chunlong Ma, Jun Wang
Summary: The COVID-19 pandemic has led to a significant interest in antiviral drug discovery. Recent studies have identified two natural compounds, dieckol and PGG, as potential SARS-CoV-2 M-pro inhibitors. However, further research has shown that neither compound inhibits M-pro, but PGG does inhibit SARS-CoV-2 PLpro. Unfortunately, PGG also exhibits cytotoxicity. Additionally, other compounds previously reported as SARS-CoV-2 PLpro inhibitors were found to be ineffective.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Chemistry, Medicinal
Chunlong Ma, Yanmei Hu, Yuyin Wang, Juliana Choza, Jun Wang
Summary: The global COVID-19 pandemic has highlighted the urgent need for effective antiviral drugs. This study focused on the development of inhibitors for the papain-like protease (PLpro), an important drug target due to its role in viral replication and host immune response. By screening a bioactive compound library, three compounds (EACC, KY-226, and tropifexor) were identified as potent PLpro inhibitors. Tropifexor, in particular, showed antiviral activity against SARS-CoV-2 in cells without causing cytotoxicity. These findings suggest that tropifexor has the potential to be further developed as an antiviral drug against SARS-CoV-2.
ACS INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Kimberly Gomez, Cheng Tang, Bin Tan, Samantha Perez-Miller, Dongzhi Ran, Santiago Loya, Aida Calderon-Rivera, Harrison J. Stratton, Paz Duran, Kyleigh A. Masterson, Anna T. Gabrielsen, Omar Alsbiei, Angie Dorame, Maria Serafini, Aubin Moutal, Jun Wang, Rajesh Khanna
Summary: In this study, a library of compounds that inhibit T-type calcium channels was synthesized and screened, leading to the discovery of a novel blocker with in vivo efficacy against various types of pain.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Chemistry, Medicinal
Jun Wang, Md Shahed-AI-Mahmud, Angelo Chen, Kan Li, Haozhou Tan, Ryan Joyce
Summary: The current monkeypox outbreaks during the COVID-19 pandemic have sparked renewed interest in antiviral drugs for orthopoxviruses. This perspective aims to summarize the antiviral activity, mechanism of action, and resistance mechanisms of orthopoxvirus antivirals to facilitate the development of additional drugs. The goal is to provide insights for medicinal chemists to prioritize drug targets and candidates for further development, thereby speeding up the discovery of orthopoxvirus antiviral drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Virology
Joshua Frost, Michael J. Rudy, J. Smith Leser, Haozhou Tan, Yanmei Hu, Jun Wang, Penny Clarke, Kenneth L. Tyler
Summary: Recent outbreaks of EV-D68 in 2014, 2016, and 2018 have led to over 600 cases of a paralytic illness called AFM. AFM primarily affects children, lacks an FDA-approved treatment, and shows limited recovery from limb weakness in many patients.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Noah H. Somberg, Joao Medeiros-Silva, Hyunil Jo, Jun Wang, William F. Degrado, Mei Hong
Summary: This study used solid-state NMR to measure the binding distance between 5-(N,N-hexamethylene) amiloride (HMA) and the envelope protein (E) of SARS-CoV-2. The results showed that HMA binds to E with a stoichiometry of one drug per pentamer and is located on the lipid-facing surface of the protein. These findings provide insights into the inhibition mechanism of HMA for SARS-CoV-2 E.
Letter
Cell Biology
Michael Dominic Sacco, Yanmei Hu, Maura Verenice Gongora, Flora Meilleur, Michael Trent Kemp, Xiujun Zhang, Jun Wang, Yu Chen
Meeting Abstract
Biophysics
Ankan Nath, Soohyun Lee, Trivikram R. Molugu, Jun Wang, Andrey V. Struts, Michael F. Brown
BIOPHYSICAL JOURNAL
(2022)
Article
Chemistry, Medicinal
Chunlong Ma, Jun Wang
Summary: The study aimed to validate a range of compounds as SARS-CoV-2 PLpro inhibitors, but results showed that these compounds did not exhibit effective inhibition of PLpro at both enzymatic and cellular levels. Therefore, further efforts are needed to search for more potent and specific SARS-CoV-2 PLpro inhibitors.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)