1 00:00:02,669 --> 00:00:07,830 COVID-19 has spread rapidly around the world, causing a pandemic that threatens global public 2 00:00:07,830 --> 00:00:15,130 health. To this day, it remains uncontrolled. COVID-19 is caused by SARS-CoV-2, a novel 3 00:00:15,130 --> 00:00:20,789 beta coronavirus. Like other coronaviruses, SARS-CoV-2 has four structural proteins, 4 00:00:21,289 --> 00:00:26,550 with the spike protein being absolutely essential for viral entry. Upon entering the body, 5 00:00:26,910 --> 00:00:31,390 SARS-CoV-2 gains access to host cells through the binding of its spike protein to the host 6 00:00:31,390 --> 00:00:37,729 receptor ACE2. Cleavage and activation of the spike protein by host proteases enables membrane 7 00:00:37,729 --> 00:00:44,009 fusion and the viral RNA is released into the cell. The host cell and its machinery are hijacked 8 00:00:44,009 --> 00:00:50,689 to facilitate viral replication and translation of essential proteins. Ultimately new virions are 9 00:00:50,689 --> 00:00:57,090 assembled and released. SARS-CoV-2 infection does not go unnoticed within the host with innate 10 00:00:57,090 --> 00:01:03,270 immune sensors able to recognize viral elements such as RNA and proteins, leading to the activation 11 00:01:03,270 --> 00:01:09,329 of an interferon-dependent antiviral response. A characteristic of SARS-CoV-2 infection is the 12 00:01:09,329 --> 00:01:15,489 large latitude of associated symptoms, from asymptomatic through to death. One reason may 13 00:01:15,489 --> 00:01:20,849 be the varying immune responses between patients, with mild cases assumed to have an effective 14 00:01:20,849 --> 00:01:27,170 response. However, SARS-CoV-2 has evolved ways to interfere with this interferon-dependent response, 15 00:01:27,629 --> 00:01:33,129 causing an unbalanced and excessive pro-inflammatory response. In the more severe 16 00:01:33,129 --> 00:01:39,329 cases of COVID-19, this may lead to a cytokine storm and hyper-inflammation with the overexpression 17 00:01:39,329 --> 00:01:45,810 of pro-inflammatory cytokines. One promising strategy to treat severe COVID-19 is the blocking 18 00:01:45,810 --> 00:01:50,569 of these inflammatory signaling pathways, using therapeutics routinely used in the clinic, 19 00:01:50,849 --> 00:01:52,069 such as dexamethasone. 20 00:01:53,069 --> 00:01:56,109 But how do we target treatment towards SARS-CoV-2? 21 00:01:57,670 --> 00:02:01,810 The initial strategy to fast-track a treatment was the repurposing of approved drugs, 22 00:02:02,049 --> 00:02:05,670 with the potential to act on the early stages of SARS-CoV-2 infection. 23 00:02:06,609 --> 00:02:11,210 Such drugs included the antiviral remdesivir, which targets viral replication. 24 00:02:12,050 --> 00:02:15,909 But after months of trials, repurposed drugs have had a limited success 25 00:02:15,909 --> 00:02:17,949 and have been proven to not be enough. 26 00:02:17,949 --> 00:02:23,250 Therefore, there remains a vital need for the development of novel therapeutics, 27 00:02:23,530 --> 00:02:25,469 specifically targeting SARS-CoV-2. 28 00:02:26,629 --> 00:02:31,169 Scientists are exploring a number of ways to disrupt the viral entry and replication cycle, 29 00:02:31,689 --> 00:02:34,449 using computational screening of small molecule libraries, 30 00:02:34,930 --> 00:02:39,169 as well as isolation and production of neutralizing antibodies from recovered patients. 31 00:02:39,930 --> 00:02:42,650 Furthermore, these antibodies can be used in combination, 32 00:02:42,849 --> 00:02:46,990 with cocktails consisting of two or more different spike-targeting antibodies 33 00:02:46,990 --> 00:02:49,550 emerging as very promising therapeutics. 34 00:02:50,569 --> 00:02:53,590 Looking to the future, we need a preventative strategy, 35 00:02:54,189 --> 00:02:57,750 and thus there is an urgent need for a vaccine against SARS-CoV-2, 36 00:02:58,150 --> 00:03:01,090 with it playing a significant role in curbing viral spread. 37 00:03:01,949 --> 00:03:05,289 Currently, scientists are exploring all the potential strategies 38 00:03:05,289 --> 00:03:07,129 to develop an efficient vaccine, 39 00:03:07,650 --> 00:03:11,610 aiming to induce neutralising antibodies against essential viral proteins, 40 00:03:11,610 --> 00:03:12,789 such as the spike. 41 00:03:13,810 --> 00:03:16,969 The more advanced vaccine candidates moving into clinical trials 42 00:03:16,969 --> 00:03:20,270 include non-replicating viral vector-based vaccines 43 00:03:20,270 --> 00:03:23,069 as well as novel mRNA-based vaccines. 44 00:03:24,009 --> 00:03:25,550 We are only at the beginning. 45 00:03:26,610 --> 00:03:28,650 There is a tremendous need to increase our knowledge 46 00:03:28,650 --> 00:03:30,509 of the SARS-CoV-2 infection cycle 47 00:03:30,509 --> 00:03:33,490 and the cellular recognition pathways involved, 48 00:03:34,270 --> 00:03:37,110 as well as the varying immune responses in COVID-19. 49 00:03:38,629 --> 00:03:41,530 Invivagen is assisting in the continuing global research effort 50 00:03:41,530 --> 00:03:42,490 on SARS-CoV-2, 51 00:03:43,009 --> 00:03:45,110 with the answers to these fundamental questions 52 00:03:45,110 --> 00:03:49,629 ultimately needed for the development of safe and effective therapeutics and vaccines.