U.S. releases in-depth report to take stock of potential treatments for new coronaviruses

This report not only describes a variety of "old drug new" candidate therapies, but also based on patent information related to coronavirus research, the early development of small molecular compounds, antibodies, cytokines, RNA therapies, and vaccines are full of dry goodsThe authors say the information in this report provides a solid knowledge base for ongoing therapeutic and vaccine development activitiesToday, the Drug Mindeand Content team will share with readers the main content of this report on potential therapieskey proteins in coronavirus infections and their function
the target of the discovery is an important step in the development of highly targeted-specific drugs and/or "old-fashioned" treatments for new coronavirus infectionsThe table below lists potential targets in the process of coronavirus infection, their role in viral infections, and some representative existing or candidate therapies for these targetsdrug Mingconde Content team mapping3CLpro and PLpro are two viral proteases that cut viral peptides into functional units to assist viruses in the process of intracellular replication and packagingVarious anti-HIV drugs target this mechanism, such as Lopinavir and LitonavirRdRp is an RNA polymerase responsible for viral RNA synthesis that can be blocked by existing antiviral and candidate drugs, including ridsievirthe interaction between the virus S protein and the host ACE2 receptor, causing the cell to swallow the virus into the cell through the inletThe broad-spectrum antiviral drug Abidore, which aims to prevent the virus from entering host cells, has had an effect on the treatment of influenzaThe TMPRSS2 protease produced by thehost plays an important role in the protein hydrolysis treatment of the S protein, which promotes the binding of the S protein to the ACE2 receptorIn in vitro trials, the TMPRSS2 inhibitor, mesulfonate, which has been validated in clinical trials, was able to block the entry of new coronaviruses into human cellsACE2 plays an important role in regulating blood pressure and the balance of fluids and electrolytes in the body, in addition to being a receptor for neo-coronavirus invasionACE2 catalytic angiotensin II degrades into angiotensin Angiotensin II acts as a constriction of blood vessels by binding to AT1 receptors, while angiotensin acts as a consonant blood vessel by binding to AT2 receptors The balance between angiotensin II and angiotensin is essential Candidate drugs targeted at these targets (e.g L-163491: partial AT1 receptor binders and partial AT2 receptor agonists) may relieve lung damage caused by neo-coronaviruses patent and drug candidates related to key target proteins
through a search of the American Chemical Society's patent database and compound database, the researchers found a number of patents and therapeutic compounds related to the key proteins mentioned above Among them, 3CLpro and RdRp two targets attracted more research and development personnel attention, targeting their potential compounds also more This may be because SARS coronaviruses also contain 3CLpro and RdRp the "old drug" for the treatment of COVID-19
because the new coronavirus is a newly discovered pathogen, there is no specific drug against it Therefore, "old medicine new use" has become a short-term economic and effective therapeutic development strategy Based on the genome sequence of the new coronavirus and the protein structure, researchers are rapidly experimenting with a range of existing drugs to treat COVID-19 patients The table below summarizes the information on these drugs and the potential mechanisms for their activity in view of the "new use of old medicine" has been introduced in a number of articles, this article will not be repeated small molecular compounds targeted at key protein targets in the development pipeline
in addition to a variety of commercial antiviral drugs, many small molecular compounds are currently in the research and development stage for a variety of key proteins of SARS and MERS viruses have produced significant inhibitory effects Most of these candidate drugs inhibit viral protease seines or RdRp Because of the high level of similarity between neo-coronavirus and SARS coronavirus These compounds may be used to treat neo-coronavirus infections These include benzopurpurin B, C-467929, C-473872, NSC-306711 and N-65828 N-65828 is a viral RNA endoenzyme inhibitor called NSP15 that reduces the infection of SARS virus in cell culture a small molecular compound that targets key targets in the pipeline (Photo: Source: Supplied) compounds C21 and CGP-42112A are two AT2 receptor agonists L-163491 has a dual effect and is a partial antagonist of the AT2 receptor and part of the antagonist of the AT1 receptor the strategy of finding other small molecular compounds
in addition to these compounds, there may be other small molecular compounds with potential therapeutic and pharmacological activity against coronaviruses based on the compounds, the researchers screened the CAS compound registry and found small molecular compounds that were 60 percent structurally similar to the compounds and conformed to the Lipinski's rule 5 The table below lists some of the compounds that are labeled with specific pharmacological activity or therapeutic uses image source: Resources Although these compounds need more research to prove their effectiveness, this search suggests a strategy for rapid discovery of potential coVID-19 therapies biological products for the treatment of coronavirus-related diseases
the use of biological products can broaden treatment options for COVID-19 and draw on the research experience gained during SARS and MERS outbreaks Based on a search of the CAS database, the researchers found more than 500 patent applications describing the use of four different biological products to treat or prevent SARS and MERS The most vaccines were developed (363), followed by therapeutic antibodies (99), interference RNA (35) and cytokines (22) antibody information for treatment/diagnosis of SARS and MERS is described in antibody 99 antibody patents Of these, 23 were SARS-specific antibodies, 17 were MERS-specific antibodies and 21 were diagnostic antibodies The table below lists the target analysis of therapeutic antibodies in the study of SARS virus The results showed that more than 90% of the antibody-targeted virus's S protein (including the receptor binding domain) These data show that the S protein is a potential target for the development of new coronavirus antibodies analysis of potential antibody therapy for SARS (Photo: Source: Supplied) 38 other patents related to other antiviral antibodies that may have an effect on the treatment of SARS or MERS This includes targeted antibodies for cytokines and chemokines such as IL-6/IL-6R, TLR3, CD16, ITAM, DC-SIGN, ICAM-3, IP-10/CXCL10, MCP.1 and other cytokines and chemokines Cytokine storms are thought to be associated with the severity of the disease in patients with COVID-19 Patients in the Intensive Care Unit (ICU) usually promote elevated levels of inflammatory cytokines Antibodies targeted at these factors may reduce the patient's inflammatory response cytokines cytokines are small molecular weight proteins that mediate the immune response to pathogens The level of production of different cytokines is critical to the body's ability to eliminate invasive pathogens In the event of a viral infection, the most significant cytokine produced by the body is interferon (IFNs), which can affect the replication of the virus Because of this function, interferon and interferon fusion proteins have been used to treat viral infections over the past 20 years The researchers found that a number of patents related to the use of interferontoms to treat SARS infections, including recombinant interferon, IFN-to-o, IFN-1, 2,3, and interferon-human serum albumin fusion proteins RNA therapy
RNA Interference (RNAi) is a natural biological process in which small RNA sequences are combined together by specific sequences on domain mRNA to inhibit gene expression or translation Since the discovery of rnAi in the 1990s, it has become a common means of silence/inhibition of genes associated with viral toxicity and pathological occurrence There are 35 patents in the CAS database relating to the use of RNAi to treat SARS infections Of these, 28 patents use siRNA and 3 use antonym oligonucleotides (ASO) The advantage of siRNA is that it can target a variety of virus-related genes, and the siRNA-targeted viral genes developed in patents include S, M, N, E genes, and genes that encode RNA polymerases the authors of the , the outbreak of COVID-19 proves once again that RNA viruses can pose a serious threat to the health of people around the world through mutation and genetic recombination, as well as cross-species transmission Even after SARS and MERS outbreaks, the world still lacks effective means to control the current OUTBREAK of COVID-19 we must work together to develop effective drugs and vaccines for existing and future potential coronavirus infections in order to reduce their impact on global health systems and human life Due to time constraints, the current "old drug new use" has become the main means of treating COVID-19 However, long-term drug development goals should include treatments that can have broad-spectrum effects on different coronaviruses, as well as means of alleviating disease symptoms and preventing death The potential drugs listed in this report could be the starting point for future drug development References: Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases ACS Cent Sci., https://doi.org/10.1021/acscentsci.0c00272 can old drugs take down a new coronavirus? Retrieved March 15, 2020, from https://cen.acs.org/sections/coronavirus/biological-chemistry/infectious-disease/coronavirus-drug-repurposing.html original title: Dry! American Chemical Society releases in-depth report to take stock of potential treatments for new coronaviruses