Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2.
Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2. Protein Cell. 2020 Aug 04;: Authors: Xiong R, Zhang L, Li S, Sun Y, Ding M, Wang Y, Zhao Y, Wu Y, Shang W, Jiang X, Shan J, Shen Z, Tong Y, Xu L, Chen Y, Liu Y, Zou G, Lavillete D, Zhao Z, Wang R, Zhu L, Xiao G, Lan K, Li H, Xu K Abstract Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not. PMID: 32754890 [PubMed - as supplied by publisher]
Publication date: Available online 10 October 2020Source: American Journal of Kidney DiseasesAuthor(s): Shreeram Akilesh, Cynthia C. Nast, Michifumi Yamashita, Kammi Henriksen, Vivek Charu, Megan L. Troxell, Neeraja Kambham, Erika Bracamonte, Donald Houghton, Naila I. Ahmed, Chyi Chyi Chong, Bijin Thajudeen, Shehzad Rehman, Firas Khoury, Jonathan E. Zuckerman, Jeremy Gitomer, Parthassarathy C. Raguram, Shanza Mujeeb, Ulrike Schwarze, M. Brendan Shannon
Publication date: Available online 9 October 2020Source: Reumatología Clínica (English Edition)Author(s): Lina María Saldarriaga Rivera, Daniel Fernández Ávila, Wilson Bautista Molano, Daniel Jaramillo Arroyave, Alain Jasaf Bautista Ramírez, Adriana Díaz Maldonado, Jorge Hernán Izquierdo, Edwin Jáuregui, María Constanza Latorre Muñoz, Juan Pablo Restrepo, Juan Sebastián Segura Charry
CONCLUSIONS: This single practice study showed total patient contact was similar over both sample periods, but most contact in 2020 was virtual. Further longitudinal multi-practice studies to confirm these findings and describe future consultation patterns are needed to inform general practice service delivery post-COVID-19. PMID: 33032304 [PubMed - in process]
Publication date: Available online 1 October 2020Source: Academic RadiologyAuthor(s): Neo Poyiadji, Chad Klochko, Jeff LaForce, Manuel L. Brown, Brent Griffith
Curious what people think with pandemic and lack of away rotations.
Publication date: 15 February 2021Source: Personality and Individual Differences, Volume 170Author(s): Brian W. Haas, Fumiko Hoeft, Kazufumi Omura
Publication date: Available online 10 October 2020Source: Academic PediatricsAuthor(s): Bonnie Crume
Authors: Hui KK PMID: 33034297 [PubMed - as supplied by publisher]
President Donald Trump’s declaration of a national emergency is designed to speed federal support to parts of America that are struggling to prepare for a coming surge of COVID-19 cases, unlocking $50 billion in aid, giving hospitals and doctors more freedom to handle a potential tsunami of sick patients and scrambling to make tests available. In a Rose Garden press conference Friday, Trump presented the emergency measures as proof that, “No nation is more prepared or more equipped to face down this crisis.” But for epidemiologists, medical experts and current and former U.S. public health officials, the ...
Pandemics are perversely democratic. They’re nasty, lethal and sneaky, but they don’t discriminate. No matter your age, ethnicity, religion, gender, or nation, you’re a part of the pathogenic constituency. That shared vulnerability, and the resulting human collectivism—a universal response to a universal threat—is newly and vividly evident in the face of the now-global outbreak of the novel coronavirus known as 2019-nCoV. As of writing, there have been over 30,000 diagnosed cases and over 630 related deaths. A virus that emerged in a single city, Wuhan, China—indeed, in a single crowded ...