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Jin Wei Mia Madel Alfajaro Peter C. DeWeirdt Ruth E. Hanna William J. Lu-Culligan Wesley L. Cai Madison S. Strine Shang-Min Zhang Vincent R. Graziano Cameron O. Schmitz Jennifer S. Chen Madeleine C. Mankowski Renata B. Filler Neal G. Ravindra Victor Gasque Fernando J. de Miguel Ajinkya Patil Huacui Chen Craig B. Wilen 《Cell》2021,184(1):76-91.e13
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《Bioorganic & medicinal chemistry letters》2020,30(20):127472
New therapies for treating coronaviruses are urgently needed. A series of 4-anilino-6-aminoquinazoline derivatives were synthesized and evaluated to show high anti-MERS-CoV activities. N4-(3-Chloro-4-fluorophenyl)-N6-(3-methoxybenzyl)quinazoline-4,6-diamine (1) has been identified in a random screen as a hit compound for inhibiting MERS-CoV infection. Throughout optimization process, compound 20 was found to exhibit high inhibitory effect (IC50 = 0.157 μM, SI = 25) with no cytotoxicity and moderate in vivo PK properties. 相似文献
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Nighat Perveen Sabir Bin Muzaffar Mohammad Ali Al-Deeb 《Saudi Journal of Biological Sciences》2021,28(2):1417-1425
The novel coronavirus disease (COVID-19) that emerged in December 2019 had caused substantial morbidity and mortality at the global level within few months. It affected economies, stopped travel, and isolated individuals and populations around the world. Wildlife, especially bats, serve as reservoirs of coronaviruses from which the variant Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) emerged that causes COVID-19. In this review, we describe the current knowledge on COVID-19 and the significance of wildlife hosts in its emergence. Mammalian and avian coronaviruses have diverse host ranges with distinct lineages of coronaviruses. Recombination and reassortments occur more frequently in mixed-animal markets where diverse viral genotypes intermingle. Human coronaviruses have evolved through gene gains and losses primarily in interfaces where wildlife and humans come in frequent contact. There is a gap in our understanding of bats as reservoirs of coronaviruses and there is a misconception that bats periodically transmit coronaviruses to humans. Future research should investigate bat viral diversity and loads at interfaces between humans and bats. Furthermore, there is an urgent need to evaluate viral strains circulating in mixed animal markets, where the coronaviruses circulated before becoming adapted to humans. We propose and discuss a management intervention plan for COVID-19 and raise questions on the suitability of current containment plans. We anticipate that more virulent coronaviruses could emerge unless proper measures are taken to limit interactions between diverse wildlife and humans in wild animal markets. 相似文献
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Yan Li Yuhua Wan Peipei Liu Jincun Zhao Guangwen Lu Jianxun Qi Qihui Wang Xuancheng Lu Ying Wu Wenjun Liu Buchang Zhang Kwok-Yung Yuen Stanley Perlman George F Gao Jinghua Yan 《Cell research》2015,25(11):1237-1249
The newly-emerging Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans. Despite global efforts, the potential for an associated pandemic in the future cannot be excluded. The development of effective counter-measures is urgent. MERS-CoV-specific anti-viral drugs or vaccines are not yet available. Using the spike receptor-binding domain of MERS-CoV (MERS-RBD) to immunize mice, we identified two neutralizing monoclonal antibodies (mAbs) 4C2 and 2E6. Both mAbs potently bind to MERS-RBD and block virus entry in vitro with high efficacy. We further investigated their mechanisms of neutralization by crystallizing the complex between the Fab fragments and the RBD, and solved the structure of the 4C2 Fab/MERS-RBD complex. The structure showed that 4C2 recognizes an epitope that partially overlaps the receptor-binding footprint in MERS-RBD, thereby interfering with the virus/receptor interactions by both steric hindrance and interface-residue competition. 2E6 also blocks receptor binding, and competes with 4C2 for binding to MERS-RBD. Based on the structure, we further humanized 4C2 by preserving only the paratope residues and substituting the remaining amino acids with the counterparts from human immunoglobulins. The humanized 4C2 (4C2h) antibody sustained similar neutralizing activity and biochemical characteristics to the parental mouse antibody. Finally, we showed that 4C2h can significantly abate the virus titers in lungs of Ad5-hCD26-transduced mice infected with MERS-CoV, therefore representing a promising agent for prophylaxis and therapy in clinical settings. 相似文献
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Osamah Barasheed Harunor Rashid Mohammad Alfelali Mohamed Tashani Mohammad Azeem Hamid Bokhary Nadeen Kalantan Jamil Samkari Leon Heron Jen Kok Janette Taylor Haitham El Bashir Ziad A.Memish Elizabeth Haworth Edward C.Holmes Dominic E Dwyer Atif Asghar Robert Booy 《Virologica Sinica》2014,(6)
Middle East respiratory syndrome coronavirus(MERS-Co V) has emerged in the Arabian Gulf region, with its epicentre in Saudi Arabia, the host of the ‘Hajj' which is the world's the largest mass gathering. Transmission of MERS-Co V at such an event could lead to its rapid worldwide dissemination. Therefore, we studied the frequency of viruses causing influenza-like illnesses(ILI) among participants in a randomised controlled trial at the Hajj 2013. We recruited 1038 pilgrims from Saudi Arabia, Australia and Qatar during the first day of Hajj and followed them closely for four days. A nasal swab was collected from each pilgrim who developed ILI. Respiratory viruses were detected using multiplex RT-PCR. ILI occurred in 112/1038(11%) pilgrims. Their mean age was 35 years, 49(44%) were male and 35(31%) had received the influenza vaccine pre-Hajj. Forty two(38%) pilgrims had laboratory-confirmed viral infections; 28(25%) rhinovirus, 5(4%) influenza A, 2(2%) adenovirus, 2(2%) human coronavirus OC43/229 E, 2(2%) parainfluenza virus 3, 1(1%) parainfluenza virus 1, and 2(2%) dual infections. No MERS-Co V was detected in any sample. Rhinovirus was the commonest cause of ILI among Hajj pilgrims in 2013. Infection control and appropriate vaccination are necessary to prevent transmission of respiratory viruses at Hajj and other mass gatherings. 相似文献
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Ji Hye Yoon Jun Young Lee Jihye Lee Young Sup Shin Sangeun Jeon Dong Eon Kim Jung Sun Min Jong Hwan Song Seungtaek Kim Sunoh Kwon Young-hee Jin Min Seong Jang Hyoung Rae Kim Chul Min Park 《Bioorganic & medicinal chemistry letters》2019,29(23):126727
3-Acyl-2-phenylamino-1,4-dihydroquinolin-4(1H)-one derivatives were synthesized and evaluated to show high anti-MERS-CoV inhibitory activities. Among them, 6,8-difluoro-3-isobutyryl-2-((2,3,4-trifluorophenyl)amino)quinolin-4(1H)-one (6u) exhibits high inhibitory effect (IC50 = 86 nM) and low toxicity (CC50 > 25 μM). Moreover, it shows good metabolic stability, low hERG binding affinity, no cytotoxicity, and good in vivo PK properties. 相似文献