PMC:7091888 / 1413-4941 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7091888","sourcedb":"PMC","sourceid":"7091888","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7091888","text":"Introduction\nThree highly pathogenic human coronaviruses (CoVs) have been identified so far, including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and a 2019 novel coronavirus (2019-nCoV), as previously termed by the World Health Organization (WHO).1–3 Among them, SARS-CoV was first reported in Guangdong, China in 2002.4 SARS-CoV caused human-to-human transmission and resulted in the 2003 outbreak with about 10% case fatality rate (CFR),1 while MERS-CoV was reported in Saudi Arabia in June 2012.5 Even though with its limited human-to-human transmission, MERS-CoV showed a CFR of about 34.4%.2 The 2019-nCoV was first reported in Wuhan, China in December 2019 from patients with pneumonia,6 and it has exceeded both SARS-CoV and MERS-CoV in its rate of transmission among humans.7 2019-nCoV was renamed SARS-CoV-2 by Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV),8 while it was renamed HCoV-19, as a common virus name, by a group of virologists in China.9 The disease and the virus causing it were named Coronavirus Disease 2019 (COVID-19) and the virus responsible for COVID-19 or the COVID-19 virus, respectively, by WHO.3 As of March 5, 2020, a total of 95,333 confirmed cases of COVID-19 were reported, including 3,282 deaths, in China and at least 85 other countries and/or territories.7 Currently, the intermediate host of SARS-CoV-2 is still unknown, and no effective prophylactics or therapeutics are available. This calls for the immediate development of vaccines and antiviral drugs for prevention and treatment of COVID-19.\nA coronavirus contains four structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins.2,10,11 Among them, S protein plays the most important roles in viral attachment, fusion and entry, and it serves as a target for development of antibodies, entry inhibitors and vaccines.1,12–17 The S protein mediates viral entry into host cells by first binding to a host receptor through the receptor-binding domain (RBD) in the S1 subunit and then fusing the viral and host membranes through the S2 subunit.16,18,19 SARS-CoV and MERS-CoV RBDs recognize different receptors. SARS-CoV recognizes angiotensin-converting enzyme 2 (ACE2) as its receptor, whereas MERS-CoV recognizes dipeptidyl peptidase 4 (DPP4) as its receptor.20,21 Similar to SARS-CoV, SARS-CoV-2 also recognizes ACE2 as its host receptor binding to viral S protein.22 Therefore, it is critical to define the RBD in SARS-CoV-2 S protein as the most likely target for the development of virus attachment inhibitors, neutralizing antibodies, and vaccines.\nIn this study, we identified the RBD fragment in SARS-CoV-2 S protein and found that the recombinant RBD protein bound strongly to human ACE2 (hACE2) and bat ACE2 (bACE2) receptors. In addition, it blocked the entry of SARS-CoV-2 and SARS-CoV into their respective hACE2-expressing cells, suggesting that it may serve as a viral attachment inhibitor against SARS-CoV-2 and SARS-CoV infection. Moreover, we demonstrated that SARS-CoV RBD-specific polyclonal antibodies cross-reacted with SARS-CoV-2 RBD protein and inhibited SARS-CoV-2 entry into hACE2-expressing cells. We have also shown that SARS-CoV RBD-specific polyclonal antibodies could cross-neutralize SARS-CoV-2 pseudovirus infection, suggesting the potential to develop SARS-CoV RBD-based vaccine for prevention of infection by SARS-CoV-2 and SARS-CoV.","divisions":[{"label":"title","span":{"begin":0,"end":12}},{"label":"p","span":{"begin":13,"end":1664}},{"label":"p","span":{"begin":1665,"end":2714}}],"tracks":[{"project":"LitCovid-PubTator","denotations":[{"id":"92","span":{"begin":37,"end":42},"obj":"Species"},{"id":"93","span":{"begin":43,"end":56},"obj":"Species"},{"id":"94","span":{"begin":58,"end":62},"obj":"Species"},{"id":"95","span":{"begin":103,"end":158},"obj":"Species"},{"id":"96","span":{"begin":160,"end":212},"obj":"Species"},{"id":"97","span":{"begin":214,"end":222},"obj":"Species"},{"id":"98","span":{"begin":231,"end":253},"obj":"Species"},{"id":"99","span":{"begin":255,"end":264},"obj":"Species"},{"id":"100","span":{"begin":343,"end":351},"obj":"Species"},{"id":"101","span":{"begin":401,"end":409},"obj":"Species"},{"id":"102","span":{"begin":417,"end":422},"obj":"Species"},{"id":"103","span":{"begin":426,"end":431},"obj":"Species"},{"id":"104","span":{"begin":527,"end":535},"obj":"Species"},{"id":"105","span":{"begin":609,"end":614},"obj":"Species"},{"id":"106","span":{"begin":618,"end":623},"obj":"Species"},{"id":"107","span":{"begin":638,"end":646},"obj":"Species"},{"id":"108","span":{"begin":681,"end":690},"obj":"Species"},{"id":"109","span":{"begin":748,"end":756},"obj":"Species"},{"id":"110","span":{"begin":799,"end":807},"obj":"Species"},{"id":"111","span":{"begin":812,"end":820},"obj":"Species"},{"id":"112","span":{"begin":855,"end":861},"obj":"Species"},{"id":"113","span":{"begin":864,"end":873},"obj":"Species"},{"id":"114","span":{"begin":886,"end":896},"obj":"Species"},{"id":"115","span":{"begin":900,"end":913},"obj":"Species"},{"id":"116","span":{"begin":1016,"end":1023},"obj":"Species"},{"id":"117","span":{"begin":1216,"end":1230},"obj":"Species"},{"id":"118","span":{"begin":1459,"end":1469},"obj":"Species"},{"id":"119","span":{"begin":762,"end":771},"obj":"Disease"},{"id":"120","span":{"begin":1134,"end":1158},"obj":"Disease"},{"id":"121","span":{"begin":1160,"end":1168},"obj":"Disease"},{"id":"122","span":{"begin":1200,"end":1208},"obj":"Disease"},{"id":"123","span":{"begin":1313,"end":1321},"obj":"Disease"},{"id":"124","span":{"begin":1353,"end":1359},"obj":"Disease"},{"id":"125","span":{"begin":1655,"end":1663},"obj":"Disease"},{"id":"142","span":{"begin":1724,"end":1729},"obj":"Gene"},{"id":"143","span":{"begin":2290,"end":2321},"obj":"Gene"},{"id":"144","span":{"begin":2323,"end":2327},"obj":"Gene"},{"id":"145","span":{"begin":2374,"end":2396},"obj":"Gene"},{"id":"146","span":{"begin":2398,"end":2402},"obj":"Gene"},{"id":"147","span":{"begin":2474,"end":2478},"obj":"Gene"},{"id":"148","span":{"begin":2588,"end":2589},"obj":"Gene"},{"id":"149","span":{"begin":2517,"end":2518},"obj":"Gene"},{"id":"150","span":{"begin":1667,"end":1678},"obj":"Species"},{"id":"151","span":{"begin":2212,"end":2220},"obj":"Species"},{"id":"152","span":{"begin":2225,"end":2233},"obj":"Species"},{"id":"153","span":{"begin":2270,"end":2278},"obj":"Species"},{"id":"154","span":{"begin":2354,"end":2362},"obj":"Species"},{"id":"155","span":{"begin":2437,"end":2445},"obj":"Species"},{"id":"156","span":{"begin":2447,"end":2457},"obj":"Species"},{"id":"157","span":{"begin":2577,"end":2587},"obj":"Species"},{"id":"179","span":{"begin":2852,"end":2856},"obj":"Gene"},{"id":"180","span":{"begin":2858,"end":2863},"obj":"Gene"},{"id":"181","span":{"begin":2873,"end":2877},"obj":"Gene"},{"id":"182","span":{"begin":2980,"end":2985},"obj":"Gene"},{"id":"183","span":{"begin":3261,"end":3266},"obj":"Gene"},{"id":"184","span":{"begin":2775,"end":2776},"obj":"Gene"},{"id":"185","span":{"begin":2764,"end":2774},"obj":"Species"},{"id":"186","span":{"begin":2846,"end":2851},"obj":"Species"},{"id":"187","span":{"begin":2934,"end":2944},"obj":"Species"},{"id":"188","span":{"begin":2949,"end":2957},"obj":"Species"},{"id":"189","span":{"begin":3073,"end":3083},"obj":"Species"},{"id":"190","span":{"begin":3139,"end":3147},"obj":"Species"},{"id":"191","span":{"begin":3202,"end":3212},"obj":"Species"},{"id":"192","span":{"begin":3239,"end":3249},"obj":"Species"},{"id":"193","span":{"begin":3309,"end":3317},"obj":"Species"},{"id":"194","span":{"begin":3446,"end":3454},"obj":"Species"},{"id":"195","span":{"begin":3504,"end":3514},"obj":"Species"},{"id":"196","span":{"begin":3519,"end":3527},"obj":"Species"},{"id":"197","span":{"begin":3088,"end":3106},"obj":"Disease"},{"id":"198","span":{"begin":3376,"end":3408},"obj":"Disease"},{"id":"199","span":{"begin":3491,"end":3500},"obj":"Disease"}],"attributes":[{"id":"A92","pred":"tao:has_database_id","subj":"92","obj":"Tax:9606"},{"id":"A93","pred":"tao:has_database_id","subj":"93","obj":"Tax:11118"},{"id":"A94","pred":"tao:has_database_id","subj":"94","obj":"Tax:11118"},{"id":"A95","pred":"tao:has_database_id","subj":"95","obj":"Tax:1335626"},{"id":"A96","pred":"tao:has_database_id","subj":"96","obj":"Tax:694009"},{"id":"A97","pred":"tao:has_database_id","subj":"97","obj":"Tax:694009"},{"id":"A98","pred":"tao:has_databas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