{"id":294,"date":"2020-04-05T10:38:27","date_gmt":"2020-04-05T10:38:27","guid":{"rendered":"https:\/\/www.creativebiolabs.net\/blog\/?p=294"},"modified":"2024-02-06T03:46:18","modified_gmt":"2024-02-06T03:46:18","slug":"alternatives-to-cope-with-lengthy-clinical-development-process-for-covid-19","status":"publish","type":"post","link":"https:\/\/www.creativebiolabs.net\/blog\/alternatives-to-cope-with-lengthy-clinical-development-process-for-covid-19\/","title":{"rendered":"Alternatives to Cope with Lengthy Clinical Development Process for COVID-19"},"content":{"rendered":"<p><span style=\"font-size: 15px;\"><strong>The latest update<\/strong><strong>\u2014<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">Cases of COVID-19 in the U.S. at a Glance on April 3, 2020, which include both confirmed and presumptive positive cases of COVID-19 reported to CDC or tested at CDC since January 21, 2020<\/span><\/p>\n<ul>\n<li>Total cases: 213,144<\/li>\n<li>Total deaths: 4,513<\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\">Lately there has been an inspiring advance in the therapeutics for COVID-19 that a modified mRNA vaccine from Moderna Therapeutics started phase 1 clinical testing, which spent just 42 days to produce the first batches of the vaccine mRNA-1273. The vaccine encodes a prefusion-stabilized form of the <span style=\"color: #0000ff;\"><strong><a style=\"color: #0000ff;\" href=\"https:\/\/www.creativebiolabs.net\/search?key=SARS-CoV-2%2520(2019-nCoV)&amp;ty=product&amp;cid=0\">2019-nCoV<\/a><\/strong><\/span> (SARS-CoV-2) spike (S) protein, which brings hope mingled with concerns to scientists that its earliest time of clinical stage would be 2021, too late in the day to deal with the current pandemic, let along the numerous technical, capital or policy challenges that may occur during its clinical development and manufacture.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">Facing the challenge, pharmaceutical companies are devotedly developing other therapeutic molecules through discovery and development pipelines, some of which are approved and already used as adjunct therapies, including Fujifilm Toyama Chemical\u2019s favipiravir and Gilead\u2019s remesdivir. Other useful approaches can be monoclonal antibodies (mAbs) targeting the previous coronaviruses like severe acute respiratory syndrome (SARS) virus and Middle Eastern respiratory syndrome (MERS) virus, small interfering RNAS (siRNAs), DNA vaccines, <em>etc.<\/em>, but we all know that the real headache lies in the clinical development stages, which is too long to defeat current \u2018epidemic enemy\u2019.<\/span><\/p>\n<p><span style=\"font-size: 15px;\">Currently some measurements are taken with the aim to reverse the present situation and to deal with the next possible health crisis in advance.<\/span><\/p>\n<ul>\n<li><strong>Focused repurposing of existing drugs<\/strong><\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\">Focused repurposing of approved small-molecule compounds seems to be the most promising way to develop computational drugs targeting SARS-CoV-2 based upon the 3CL protease from the SARS virus, but there are technical limitations on the AI systems or other in silico approaches. In addition, the development process may not come to the result inspection stage when there is a lack of continued funding, or ending of the epidemic, just like the single phase 1 drug study (NCT00215826) and two phase 1 vaccine studies targeting SARS, in 2003.<\/span><\/p>\n<ul>\n<li><strong>Preparation for therapeutic mAb targeting specific pathogens in advance<\/strong><\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\">Researchers believe that, non-market mechanisms like the Platform for European Preparedness Against Re-Emerging Epidemics (PREPARE) out of Antwerp, Belgium, and the US Defense Advanced Research Projects Agency (DARPA)\u2019s Pandemic Prevention Platform (P3) program can help in that they take action in advance, of which the latter has paid attention to some mAb programs for COVID-19 that can cut down preclinical duration.<\/span><\/p>\n<p style=\"text-align: left;\"><span style=\"font-size: 15px;\">In-process Monoclonal Antibodies (mAbs) for COVID-19<\/span><\/p>\n<table width=\"552\">\n<tbody>\n<tr>\n<td width=\"159\"><strong>Company<\/strong><\/td>\n<td width=\"392\"><strong>Modality<\/strong><\/td>\n<\/tr>\n<tr>\n<td width=\"159\">AbCellera Biologics<\/td>\n<td width=\"392\">Fully human IgG1 mAbs targeting SARS-CoV-2<\/td>\n<\/tr>\n<tr>\n<td width=\"159\">EUSA Pharma<\/td>\n<td width=\"392\">Sylvant (siltuximab), human IgG1\u03ba mAb against IL-6<\/td>\n<\/tr>\n<tr>\n<td width=\"159\">ImmunoPrecise Antibodies<\/td>\n<td width=\"392\">Fully human IgG1 mAbs targeting multiple undisclosed epitopes on SARS-CoV-2<\/td>\n<\/tr>\n<tr>\n<td width=\"159\">InflaRx<\/td>\n<td width=\"392\">Fully human IgG1 mAb against complement factor 5a<\/td>\n<\/tr>\n<tr>\n<td width=\"159\">Vir Biotechnology<\/td>\n<td width=\"392\">Human IgG1 mAbs targeting SARS-CoV-2<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><span style=\"font-size: 15px;\"><strong>Mechanism of SARS-CoV-2 infecting human body determines that antibodies against specific proteins on the surface of SARS-CoV-2 are an intuitive approach.<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">The process of SARS-CoV-2 infecting normal cells can be roughly divided into three steps: invasion, genome replication and transcription, production of virus proteins and assembly of new viruses. Different proteins play varied roles in this process. For example, the spike glycoprotein (s protein) on the surface of the virus is the key for the virus to invade the host cell. Without the binding of S protein to the receptor molecules on the surface of host cells, the viral envelope could not fuse with the host cell membrane, and could not cause infection. When SARS-CoV-2 invades human body, its S protein first specifically binds to the receptor angiotensin-converting enzyme 2 (ACE2), which then translates the RNA polymerase, transcribing its own genes into mRNA and constructing other structural proteins.<\/span><\/p>\n<p><a href=\"\/blog\/wp-content\/uploads\/2020\/04\/coronavirus-LP-graphic-2.jpg\"><img decoding=\"async\" loading=\"lazy\" class=\"size-full wp-image-295 aligncenter\" src=\"\/blog\/wp-content\/uploads\/2020\/04\/coronavirus-LP-graphic-2.jpg\" alt=\"\" width=\"400\" height=\"247\" srcset=\"\/blog\/wp-content\/uploads\/2020\/04\/coronavirus-LP-graphic-2.jpg 400w, \/blog\/wp-content\/uploads\/2020\/04\/coronavirus-LP-graphic-2-300x185.jpg 300w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><\/a><\/p>\n<p><span style=\"font-size: 15px;\"><strong>Alternative mAbs that are applicable for research<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">Other therapeutic rabbit\/mouse\/humanized monoclonal antibodies of various crucial target spots of SARS-C0V-2 can join to improve the odds, including:<\/span><\/p>\n<ul>\n<li><strong><span style=\"color: #0000ff;\"><a style=\"color: #0000ff;\" href=\"https:\/\/www.creativebiolabs.net\/symbolsearch_2019-nCoV%20S%20%28RBD%29.htm\">2019-nCoV S receptor binding domain<\/a><\/span><\/strong> (RBD, responsible for recognizing the cell surface receptor.)<\/li>\n<\/ul>\n<ul>\n<li>2019-nCoV NP (N protein, required for coronavirus RNA synthesis, has RNA chaperone activity that may be involved in template switch.)<\/li>\n<\/ul>\n<ul>\n<li><strong><span style=\"color: #0000ff;\"><a style=\"color: #0000ff;\" href=\"https:\/\/www.creativebiolabs.net\/symbolsearch_2019-nCoV%20S1.htm\">2019-nCoV S1<\/a><\/span><\/strong> &amp; S2 (S1 consists a receptor binding domain; S2 composes elements required for the membrane fusion.)<\/li>\n<\/ul>\n<p><span style=\"font-size: 15px;\"><strong>\u00a0<\/strong><strong>Joint efforts should be made between pharmaceuticals and antibody engineers<\/strong><\/span><\/p>\n<p><span style=\"font-size: 15px;\">On 12 March 2020, Vir announced that Biogen committed to being its North American development and clinical manufacturing partner for the proprietary anti-SARS-CoV-2 mAbs. There is no doubt that only with the joint efforts of the government, pharmaceutical companies, and antibody manufacturers, could the clinic process be expedite, and effective drugs &amp; vaccines enter the clinic test as soon as possible.<\/span><\/p>\n<p><span style=\"color: #808080;\">Reference<\/span><\/p>\n<p><span style=\"color: #808080; font-size: 14px;\">1. Simonian M, &#8220;Covid-19 Vaccines, Immunity, And Effect On Children.&#8221; Medicine and Healthcare Reports 2.4 (2021).<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The latest update\u2014 Cases of COVID-19 in the U.S. at a Glance on April 3, 2020, which include both confirmed and presumptive positive cases of COVID-19 reported to CDC or tested at<a class=\"moretag\" href=\"https:\/\/www.creativebiolabs.net\/blog\/alternatives-to-cope-with-lengthy-clinical-development-process-for-covid-19\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":295,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3],"tags":[47,45,6],"_links":{"self":[{"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/posts\/294"}],"collection":[{"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/comments?post=294"}],"version-history":[{"count":11,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/posts\/294\/revisions"}],"predecessor-version":[{"id":452,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/posts\/294\/revisions\/452"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/media\/295"}],"wp:attachment":[{"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/media?parent=294"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/categories?post=294"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.creativebiolabs.net\/blog\/wp-json\/wp\/v2\/tags?post=294"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}