Discovery of M2 channel blockers targeting the drug-resistant double mutants M2-S31N/L26I and M2-S31N/V27A from the influenza A viruses.

In this study, we identified four amantadine-resistant M2 mutants among avian and human influenza A H5N1 strains circulating between 2002 to 2019: the single S31N and V27A mutants, and the S31N/L26I and S31N/V27A double mutants. Herein, utilizing two-electrode voltage clamp (TEVC) assays, we screened a panel of structurally diverse M2 inhibitors against these single and double mutant channels. Three compounds 6, 7, and 15 were found to significantly block all three M2 mutants: M2-S31N, M2-S31N/L26I, and M2-S31N/V27A. Using recombinant viruses generated from reverse genetics, we further showed that these compounds also inhibited the replication of recombinant viruses harboring either the single S31N or double S31N/L26I and S31N/V27A mutants. This work represents the first example in developing antivirals by targeting the drug-resistant double mutants of M2 proton channels. PMID: 31669761 [PubMed - as supplied by publisher]
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research

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Over the past few years, Professor Zhang Yongzhen has made it his business to sequence thousands of previously unknown viruses. But he knew straight away that this one was particularly nasty. It was about 1:30 p.m. on Jan. 3 that a metal box arrived at the drab, beige buildings that house the Shanghai Public Health Clinical Center. Inside was a test tube packed in dry ice that contained swabs from a patient suffering from a peculiar pneumonia sweeping China’s central city of Wuhan. But little did Zhang know that that box would also unleash a vicious squall of blame and geopolitical acrimony worthy of Pandora herself....
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized COVID-19 overnight Source Type: news
Over the past few years, Professor Zhang Yongzhen has made it his business to sequence thousands of previously unknown viruses. But he knew straight away that this one was particularly nasty. It was about 1:30 p.m. on Jan. 3 that a metal box arrived at the drab, beige buildings that house the Shanghai Public Health Clinical Center. Inside was a test tube packed in dry ice that contained swabs from a patient suffering from a peculiar pneumonia sweeping China’s central city of Wuhan. But little did Zhang know that that box would also unleash a vicious squall of blame and geopolitical acrimony worthy of Pandora herself....
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized COVID-19 overnight Source Type: news
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Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized COVID-19 feature Magazine Source Type: news
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Source: Virology Journal - Category: Virology Authors: Tags: Research Source Type: research
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Source: Critical Reviews in Microbiology - Category: Microbiology Authors: Tags: Crit Rev Microbiol Source Type: research
“Everyone knows that pestilences have a way of recurring in the world,” observes Albert Camus in his novel The Plague. “Yet somehow we find it hard to believe in ones that crash down on our heads from a blue sky. There have been as many plagues as wars in history; yet plagues and wars always take people by surprise.” Camus was imagining a fictional outbreak of plague in 1948 in Oran, a port city in northwest Algeria. But at a time when the world is reeling from a very real microbial emergency sparked by the emergence of a novel coronavirus in Wuhan, central China, his observations are as pertinent a...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized 2019-nCoV health ideas Source Type: news
People wear face masks in the waiting area at China's Shenzhen Bao'an International Airport. Credit: UN News/Jing ZhangBy Fairuz AhmedNEW YORK, Feb 3 2020 (IPS) We are now living in a hyper communicative world where news does travel faster than lightning. Boundaries, borders, geographical and time differences have become next to obsolete in today’s speed driven world. At any point in time people, news and local occurrences can influence internationally without much local isolation. Along with the advantages of technology, communications and connections world is also facing new challenges that are proportionally evolv...
Source: IPS Inter Press Service - Health - Category: International Medicine & Public Health Authors: Tags: Asia-Pacific Economy & Trade Headlines Health Humanitarian Emergencies Population TerraViva United Nations Source Type: news
Abstract The highly pathogenic avian influenza (HPAI) H5N1 viruses and their spillover into the human population pose substantial economic and public health threats. Although antiviral drugs have some effect in treating influenza infection, vaccination is still the most effective intervention to prevent possible pandemic outbreaks. We have developed a novel H5 influenza vaccine to improve the world's pandemic preparedness. We produced a hemagglutinin (HA) of HPAI H5N1 virus A/Alberta/01/2014 (AB14) using both mammalian (m) and bacterial (b) expression systems. The purified recombinant proteins were formulated with...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
Conclusions: Human challenge studies and systems biology approaches are important tools that should be used in concert to advance our understanding of influenza infection and provide targets for novel therapeutics and immunizations. Introduction Although influenza virus was recognized as an important pathogen over a century ago, influenza continues to cause a significant burden of disease. In the United States alone, it's estimated that in the 2017–2018 season there were 959,000 hospitalizations related to influenza illness, and 79,400 deaths (CDC, 2018). Worldwide, WHO estimates that annual influenza...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Jennifer M. Rudd1, Sivasami Pulavendran1, Harshini K. Ashar1, Jerry W. Ritchey1, Timothy A. Snider1, Jerry R. Malayer1, Montelongo Marie1, Vincent T. K. Chow2 and Teluguakula Narasaraju1* 1Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, United States2Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore Exaggerated host innate immune responses have been implicated in severe influenza pneumonia. We have previously demonstrated that excessive neutrophils recruited during in...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
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