Research & Development on Therapeutic Agents and Vaccines for Covid-19
Abstract
Since the Covid-19 outbreak began, this new respiratory infection has spread very quickly globally. Preparing for what could possibly be a pandemic, researchers and doctors have been on the clock trying to grasp what this new deadly virus is, understanding the pathophysiology behind it, to see if new therapies and vaccines can be uncovered.
American Chemical Society (ACS) is presenting a special report on this new virus as it gives support to present day research and development. (ACS) will go behind the scenes on giving a summary of new scientific journal information, focusing on patents and (ACS) content collection. (ACS) points out antiviral ways, where miniscule molecules and biologics going after complicated molecular communication between coronavirus and infection. Then comes the drug-repurposing effort that has been reported, zeroing in on main agents that are known to be effective on overcoming other RNA viruses (that includes SARS and MERS). The coronavirus biologics includes the following: therapeutic antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression, and other vaccine types.
Over 500 patents talk about methodologies on 4 biologics, with the ability of treating and minimizing the occurrence of coronavirus infections, relevant to Covid-19. The data given in this article gives a robust intellectual foundation, on laying out the ongoing quest on uncovering therapies and vaccines.
Background
Covid-19, a.k.a. (also known as), the novel coronavirus disease, is caused by 2019-nCov, with an official designated status as a type of severe acute respiratory syndrome-related coronavirus, known as SARS-CoV-2. This new respiratory infection poses a pandemic threat worldwide. It started in Wuhan, Hubei Province China, the epicenter and origin of the outbreak, back in December 2019. This disease has transmitted to over 100 nations, with more than 100,000 confirmed cases, and more than 3,800 mortalities globally, from March 9, 2020 figures. Also, many people’s lives have been affected due to strict obligatory isolations and quarantines. This roller coaster effect on the Covid-19 outbreak can lead to HUGE obstacles globally on the health systems everywhere, and have drastic consequences on the world economy if the virus is not curbed and brought under control.
Novel Coronavirus
So, what is a coronavirus? They are pretty big viruses, having a single strand RNA, enclosed inside the membrane envelope. This membrane inside the virus has glycoprotein spikes, which resemble a crown. Coronaviruses are known to infect BOTH people and animals; but certain animals, such as bats, carry LARGE quantities of coronaviruses, and appear to have immunity on illnesses related to coronavirus. The following 4 classes of coronaviruses are alpha, beta, gamma, and delta. The betacoronavirus category consist of severe acute respiratory syndrome (SARS) virus ((SARS-CoV), Middle East respiratory syndrome (MERS) virus (MERS-CoV), and the COVID-19 culprit agent, SARS-CoV-2. Resembling SARS and MERS, Covid-19 goes after the lower respiratory region, which gives viral pneumonia, but also affects the GI (gastrointestinal) region, heart, kidney, liver, and CNS (central nervous system), which leads to organ failure in more than 1 organ. Present day information shows that Covid-19 is far more contagious and deadly than SARS.
The Viral Genome
The genome for betacoronavirus conceals multiple structural proteins, which also comprises of the glycosylated spike (S) protein that serves as a big trigger on the host immune reactions. S protein interferes with host cell in BOTH SARS and Covid-19 by sticking to a receptor protein, known as angiotensin-converting enzyme 2 (ACE2), which is inside the surface membrane of the host cell. A study recently showed that this interfering process needs S protein priming which is aided by the host cell, makes serine protease TMPRSS211. Also, viral genome conceals multiple nonstructural proteins, which comprises of RNA-dependent RNA polymerase (RdRp), coronavirus main protease (3CLpro), and papain-like protease (Plpro). In addition, PLpro behaves as a deubiquitinase, which can probably deubiquinate specific host cell proteins, including interferon factor 3 and NF-κB, leading to immune suppression. RdRp makes full-length negative-strand RNA template, which is used by RdRp to produce more viral genomic RNA.
The communication with S viral protein and ACE2 with host cell surface, attracts plenty of interest because it is the site of location that starts the infection process. Cyro-EM structure analysis shows that the affinity to stick to a Covid-19 S protein to ACE2 is approximately 10-20x increased compared to a SARS protein. There is speculation that this can probably lead to increased transmission and contagiousness for Covid-19, compared to SARS.
Therapeutic Agents?
The investigation also applies on uncovering therapeutic agents going after the very conserved proteins having to do with SARS and Covid-19. RdRp and 3CLpro protease of SARS-CoV-2 have over 95% of sequence resemblance with those of SARS even though these two viruses have only 79% sequence resemblance on the genome level. Also, even though PLpro sequences of SARS-CoV-2 and SARSCoV have 83% resemblance, both have resembling active sites.
Up until now, there has not been any Covid-19 antiviral agents. Scientists are racing against the clock on coming up with potential treatments to rescue many lives and come up with vaccines for prevention in the near future. (ACS) did an analysis on scientific information associated with the development in therapeutic agents and vaccines for Coronavirus going back to 2003. Hence, they are supporting research and development efforts on uncovering powerful therapeutic and preventive agents related to Covid-19. The analysis given in this article are from the (ACS) content collection. It includes a scientist-curated data collection that addresses scientific journal articles and patents published from more than 60 recognized patent agencies globally. Regarding a subset of the analysis, (ACS) and Medline data were analyzed on a collective basis.
Summary and Perspectives
This article summarized scientific journal information published on worldwide research and development, related to coronavirus therapies, and vaccines from the vast content collection, with emphasis on patents. It touched on the following areas: coronavirus morphology, biology, and pathogenesis with a particular focus on antiviral strategies involving small molecule drugs, along with biologics targeting complex molecular communications associated with coronavirus infection and replication. Drug-repurposing efforts in this article focuses mainly on agents that are presently known to be effective on overcoming other RNA viruses ( SARS, MERS, influenza, HCV, and Ebola as well as antiinflammatory drugs). The potential impact regarding biologics for coronavirus treatment shows hope, and has many options, including the following: bioengineered and vectored antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression, and many types of vaccines.
The data given in this article, shows robust intellectual foundation in supporting continued research and development in discovering and developing therapies and vaccines related to Covid-19 and other diseases related to the coronavirus. This article touches on minimal attention on present day efforts related on the advancement, efficiency, and accurate Covid-19 diagnosis methods and products.
Novel infectious ailments from RNA viruses, prone to mutation and genetic recombination, along with cross-species transmission, will play a continuing role to demonstrate severe worldwide health intimidation, as seen in Covid-19. Even with the 2 former coronavirus outbreaks (SARS and MERS), around the globe, we are far from prepared in managing effectively the present day Covid-19 outbreak. Moreover, it has already been documented and reported that Covid-19 has led to many mortalities across the globe.
Seeking a Treatment
Conscious efforts on coming up with effective medications and vaccines in overcoming what could be potentially future coronavirus infections, and current infections taking place, as well as potent pathogenic outbreaks is needed on decreasing the costly effect on human lives and healthcare systems worldwide. Taking into consideration the expensive and laborious process that is needed with clinical drug development, the Covid-19 outbreak shows the value on coming up with relatively broad-spectrum antiviral medications, and how crucial it is to come up with innovative ways (AI, or artificial intelligence) on leading to uncovering a new treatment.
With the long process of coming up with a new drug, the present day way on drug repurposing has been seen as one of the preferred methods for speedy treatment on Covid-19 infected patients. Goals for long-term development in the business of the pharmaceutical companies comprise of the following: identification of inhibitors focused on replication or infection processes associated with SARS-CoV-2 or other related coronaviruses, and the symptomatic results of their infections resulting in severe disease and/or death.
Vaccines and Trials
This summary shows minuscule molecule compounds, and other blurbs written of biologics, containing properties that would be fit for blocking several major coronavirus proteins, and can function as a starting point on developing medications. Given vaccines are important in preventing coronavirus related ailments in the near future, it is comforting to know that many innovative strategies are being implemented. There have been 4 MERS DNA vaccine participants starting Phase 1 clinical trials from September 2019. Moderna Inc., just published the 1st set of mRNA-1273 back in February 2020 (mRNA vaccine to overcome Covid-19, which is ready for Phase 1 clinical use here in the US).
Conclusion
More joint partnerships from across the globe, focusing on the aspects of antiviral discovery progress and clinical trial results, will benefit everyone’s ability to look up potential medications that demonstrate therapeutic potential, and decrease time needed to bring these medications to the market. Ample publications and a quick publishing pace related to Covid-19 regarding the coronavirus infection and outbreak, as demonstrated in this article, are suggestive regarding the HUGE time put into by recognized research institutes, and pharmaceutical companies, on presenting BOTH molecular mechanism and practical therapies on remedying present and future coronavirus epidemics.