Article
Virology
Lars Pelz, Elena Piagnani, Patrick Marsall, Nancy Wynserski, Marc Dominique Hein, Pavel Marichal-Gallardo, Sascha Young Kupke, Udo Reichl
Summary: This study demonstrates that influenza A virus defective interfering particles (DIPs) can suppress the replication and spread of respiratory syncytial, yellow fever, and Zika viruses in human lung cells. The antiviral activity of DIPs is dependent on the production of interferon and the activation of the JAK/STAT signaling pathway.
Article
Microbiology
Paulina Koszalka, Ankita George, Vijaykrishna Dhanasekaran, Aeron C. Hurt, Kanta Subbarao
Summary: Combination therapy with influenza drugs baloxavir and oseltamivir can reduce the selection of viruses with reduced drug susceptibility. In animal models, combination therapy and monotherapy have similar effectiveness in reducing viral titers, but combination therapy can decrease the selection of viruses with reduced susceptibility to baloxavir.
Article
Virology
Bao Lyu, Chang Wang, Yuanyuan Bie, Jing Kong, An Wang, Liang Jin, Yang Qiu, Xi Zhou
Summary: This study demonstrates that enoxacin can enhance RNAi in insects and has potent antiviral effects against diverse viruses in fruit flies and mosquitoes.
JOURNAL OF VIROLOGY
(2022)
Article
Nanoscience & Nanotechnology
Seokoh Moon, Jinhyo Chung, Yuna Kim, Celab Hong, Soomin Kim, Jaehyeon Hwang, Younghun Jung, Woo-Jae Chung, Dae-Hyuk Kweon
Summary: Researchers created hetero di-discs by connecting nanodiscs loaded with different receptors, for broad-spectrum antiviral activity. The hetero di-discs showed strong antiviral activity in vitro and in vivo, and enabled delivery of multiple ligands without interference.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2022)
Review
Virology
Yaqin Bai, Jeremy C. Jones, Sook-San Wong, Mark Zanin
Summary: Hemagglutinin and neuraminidase are critical parts of influenza viruses, serving as targets for immune response and antiviral drugs. Neuraminidase inhibitors like oseltamivir are commonly used against influenza, while antivirals targeting hemagglutinin are newer with a higher resistance threshold.
Article
Chemistry, Multidisciplinary
Alba Monferrer, Jessica A. Kretzmann, Christian Sigl, Pia Sapelza, Anna Liedl, Barbara Wittmann, Hendrik Dietz
Summary: This study reports a virus encapsulation platform based on DNA origami structures that can effectively trap a broad range of viruses by exploiting the affinity and attachment of viruses to heparan sulfate proteoglycans. The DNA origami shells can encapsulate multiple virus particles and prevent further interactions with cell surface receptors.
Article
Pharmacology & Pharmacy
Evelien Vanderlinden, Arnaud Marchand, Ria Van Berwaer, Wim van Dam, Philippe Arzel, Hugo Klaassen, Leentje Persoons, Patrick Chaltin, Lieve Naesens
Summary: CPD A is a novel inhibitor of influenza A and B virus replication and RNA synthesis with broad-spectrum activity. Its mechanism of action lies between 1 and 5 h p. i., similar to ribavirin.
ANTIVIRAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Zhenyu Li, Tian Li, Meisui Liu, Tijana Ivanovic
Summary: Understanding mechanisms of resistance to antiviral inhibitors can lead to improved strategies for inhibitor design. This study found that stabilizing mutations in the fusion peptide make the virus more sensitive to Arbidol, while destabilizing mutations make the virus resistant. Fusion-peptide destabilization leads to resistance, even without reduced Arbidol binding to the virus. Arbidol increases the free-energy cost for fusion-peptide release, explaining the observed resistance.
ACS INFECTIOUS DISEASES
(2022)
Review
Microbiology
Sania Batool, Santosh Chokkakula, Min-Suk Song
Summary: Influenza infection is a serious health concern due to the constant mutation and recombination of the influenza virus. This makes it difficult to eliminate the disease and treatment challenging. Combination therapy with multiple antivirals or immunomodulators is considered the best strategy for effectively treating influenza infection. This review discusses the current options for combination therapy, their performance, and the limitations imposed by drug resistance.
Article
Virology
Sarah Al-Beltagi, Cristian Alexandru Preda, Leah Goulding, Joe James, Juan Pu, Paul Skinner, Zhimin Jiang, Belinda Lei Wang, Jiayun Yang, Ashley C. Banyard, Kenneth H. Mellits, Pavel Gershkovich, Christopher J. Hayes, Jonathan Nguyen-Van-Tam, Ian H. Brown, Jinhua Liu, Kin-Chow Chang
Summary: Thapsigargin (TG) has shown potent antiviral activity against various respiratory viruses, including RSV, OC43, SARS-CoV-2, and influenza virus, with superior performance compared to existing drugs like remdesivir. This broad-spectrum inhibitor also demonstrated lasting antiviral effects and protection against lethal influenza virus challenge in mice.
Article
Microbiology
Chiara Medaglia, Arnaud Charles-Antoine Zwygart, Paulo Jacob Silva, Samuel Constant, Song Huang, Francesco Stellacci, Caroline Tapparel
Summary: Influenza viruses have high genetic variability and can quickly develop resistance mutations. Combination therapy with two drugs can reduce the risk of resistance emergence. Combining interferon lambda with oseltamivir can delay the emergence of drug-resistant influenza virus variants.
Article
Pharmacology & Pharmacy
Jiao Hu, Lei Zhang, Xinxin Zheng, Guoqing Wang, Xia Chen, Zenglei Hu, Yu Chen, Xiaoquan Wang, Min Gu, Shunlin Hu, Xiaowen Liu, Xinan Jiao, Daxin Peng, Xiufan Liu
Summary: This study identified a functional lncRNA, LncRNA#61, as a broad anti-IAV factor. LncRNA#61 is highly upregulated by different subtypes of IAV and can translocate from the nucleus to the cytoplasm soon after IAV infection. Forced LncRNA#61 expression dramatically impedes viral replication of various subtypes of IAV, while abolishing LncRNA#61 expression substantially favors viral replication. Moreover, LncRNA#61 delivered by the lipid nanoparticle (LNP)-encapsulated strategy shows good performance in restraining viral replication in mice. Mechanistically, the four long ring arms of LncRNA#61 mainly mediate its broad antiviral effect and contribute to its inhibition of viral polymerase activity and nuclear aggregation of key polymerase components. Therefore, LncRNA#61 is defined as a potential broad-spectrum antiviral factor for IAV, providing valuable clues for developing novel anti-IAV therapeutics targeting host lncRNAs.
ANTIVIRAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Sumin Son, Soo Bin Ahn, Geonyeong Kim, Yejin Jang, Chunkyu Ko, Meehyein Kim, Sang Jick Kim
Summary: Influenza A virus continuously infects humans and the antigenic shifts of this respiratory virus threaten public health. Broadly neutralizing antibodies (bnAbs) targeting the antigenic surface glycoprotein hemagglutinin (HA) protect against various subtypes of influenza A virus. Two human monoclonal antibodies (mAbs), G1 and G2, were identified in this study, which target HA proteins of H1N1 and H3N2 subtypes, respectively. In cell culture-based assays, G1 and G2 efficiently suppressed infection of H1N1 and H3N2 subtypes. Mode-of-action studies showed that G1 blocked membrane fusion while G2 inhibited viral attachment to host cells. Both antibodies also elicited antibody-dependent cellular cytotoxicity (ADCC) activities. In mouse challenge models, single-shot administration of G1 and G2 antibodies completely protected mice from viral infections. The newly identified bnAbs, G1 and G2, provide insight into the development of broad-spectrum antivirals against future pandemic influenza A viruses.
ANTIVIRAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Aleksandr Ianevski, Shahzaib Ahmad, Kraipit Anunnitipat, Valentyn Oksenych, Eva Zusinaite, Tanel Tenson, Magnar Bjoras, Denis E. Kainov
Summary: Viral epidemics and pandemics have driven the development and discovery of both known and novel antiviral agents. Over a hundred mono- and combination antiviral drugs have been approved, with thousands more in development. Interferons and certain small molecules show broad-spectrum antiviral activity alone or in combination, which could be beneficial for treating emerging and re-emerging viral infections.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yifei Feng, Yan Yang, Shuting Zou, Shuqi Qiu, Hao Yang, Yi Hu, Guifen Lin, Xingang Yao, Shuwen Liu, Min Zou
Summary: ALA is a promising broad-spectrum antiviral agent that inhibits the infection of Zika virus, Dengue virus, herpes virus, influenza virus, and SARS-CoV-2. It disrupts the membrane integrity of the viruses, releasing viral RNA and inhibiting viral infectivity.
ANTIVIRAL RESEARCH
(2023)
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
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
Multidisciplinary Sciences
Michael D. Sacco, Shaohui Wang, Swamy R. Adapa, Xiujun Zhang, Eric M. Lewandowski, Maura Gongora, Dimitra Keramisanou, Zachary D. Atlas, Julia A. Townsend, Jean R. Gatdula, Ryan T. Morgan, Lauren R. Hammond, Michael T. Marty, Jun Wang, Prahathees J. Eswara, Ioannis Gelis, Rays H. Y. Jiang, Xingmin Sun, Yu Chen
Summary: β-lactam antibiotics inhibit bacterial cell wall synthesis by targeting PBPs. This study reveals the unique structural features of PBPs in C. difficile and sheds light on the mechanisms underlying beta-lactam resistance in this pathogen, providing new insights for the treatment of Clostridioides difficile infection.
NATURE COMMUNICATIONS
(2022)
Review
Chemistry, Medicinal
Ryan P. Joyce, Vivian W. Hu, Jun Wang
Summary: The rapid development of effective vaccines has decreased hospitalization and mortality rate. However, with the risk of mutated strains, there is an increasing demand for antivirals. Nirmatrelvir is an orally bioavailable antiviral that can be administered in outpatient settings to minimize hospitalizations and death.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Review
Chemistry, Multidisciplinary
Bin Tan, Ryan Joyce, Haozhou Tan, Yanmei Hu, Jun Wang
Summary: This article describes the development of antiviral drugs against SARS-CoV-2, including noncovalent and covalent main protease inhibitors, as well as the identification of drug-resistant mutants. It also introduces a cell-based assay for evaluating the cellular target engagement of inhibitors and provides guidance for the development of orally bioavailable Mpro inhibitors.
ACCOUNTS OF CHEMICAL RESEARCH
(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.
Article
Biochemical Research Methods
Colin J. Potter, Yanmei Hu, Zhen Xiong, Jun Wang, Euan McLeod
Summary: The global COVID-19 pandemic caused by the SARS-CoV-2 virus emphasizes the need for point-of-care diagnostic tests. Researchers have developed a portable lens-free imaging system coupled with a particle agglutination assay as a biosensor for SARS-CoV-2. This biosensor can accurately detect SARS-CoV-2 levels in complex samples, potentially mitigating the spread of the pandemic.
Article
Biology
Yanmei Hu, Chunlong Ma, Jun Wang
Summary: This study provides detailed protocols for the cytopathic effect (CPE) assay and the plaque assay for human coronaviruses, which can be used to identify novel antivirals and evaluate the antiviral activity of existing drug candidates.
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)