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Considering the potential threat of a pandemic, scientists and physicians have been racing to understand this new virus and the pathophysiology of this disease to uncover possible treatment regimens and discover effective therapeutic agents and vaccines. To support the current research and development, CAS has produced a special report to provide an overview of published scientific information with an emphasis on patents in the CAS content collection.
It highlights antiviral strategies involving small molecules and biologics targeting complex molecular interactions involved in coronavirus infection and replication. The patent analysis of coronavirus-related biologics includes therapeutic antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression as well as various types of vaccines.
More than patents disclose methodologies of these four biologics with the potential for treating and preventing coronavirus infections, which may be applicable to COVID The information included in this report provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines.
These metrics are regularly updated to reflect usage leading up to the last few days. Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts. The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.
Find more information on the Altmetric Attention Score and how the score is calculated. Figure 1. Copyright World Health Organization. Figure 2. Figure 3. Cartoon illustration of the coronavirus structure and viral receptor ACE2 on the host cell surface. Image was reproduced with permission from ref 9 , Nature Reviews Microbiology 7 3 , — Copyright Springer Nature. Over journal articles were published in the first two months of , and the number of published articles has increased each week since the week of January 13, Figure 5.
An inhibitor of viral entry to host cells. Its direct action on S protein and ACE2 is yet to be confirmed. Ritonavir is a pharmacokinetic profile enhancer that may potentiate the effects of other protease inhibitors due to its ability to attenuate the degradation of those drugs by the liver enzyme CYP3A4 and thus is used in combination with antivirial Lopinavir.
More than patents that disclose the use of four biologics classes such as therapeutic antibodies, cytokines, RNA therapies, and vaccines to treat and prevent SARS and MERS have been analyzed for this study. The American Chemical Society holds a copyright ownership interest in any copyrightable Supporting Information.
Files available from the ACS website may be downloaded for personal use only. Users are not otherwise permitted to reproduce, republish, redistribute, or sell any Supporting Information from the ACS website, either in whole or in part, in either machine-readable form or any other form without permission from the American Chemical Society.
For permission to reproduce, republish and redistribute this material, requesters must process their own requests via the RightsLink permission system. We would like to thank Dr. Gilles George for his encouragement and support for this work. More by Cynthia Liu. More by Qiongqiong Zhou. More by Yingzhu Li. More by Linda V. More by Steve P.
More by Linda J. More by Jeffrey Smoot. More by Anne C. More by Angela D. More by Susan Jervey. More by Dana Albaiu. Cite this: ACS Cent. ACS AuthorChoice. Article Views Altmetric -. Citations The outbreak of the novel coronavirus disease, COVID, caused by the new coronavirus nCoV that is now officially designated as severe acute respiratory syndrome-related coronavirus SARS-CoV-2, represents a pandemic threat to global public health.
The ripple effect of the COVID outbreak could potentially bring major challenges to worldwide health systems and have far-reaching consequences on the global economy if the spread of the virus is not effectively controlled. High Resolution Image. Coronaviruses CoVs are relatively large viruses containing a single-stranded positive-sense RNA genome encapsulated within a membrane envelope.
The viral membrane is studded with glycoprotein spikes that give coronaviruses their crown-like appearance Figure 3.
While coronaviruses infect both humans and animals, certain types of animals such as bats that host the largest variety of coronaviruses appear to be immune to coronavirus-induced illness. The betacoronavirus genome encodes several structural proteins, including the glycosylated spike S protein that functions as a major inducer of host immune responses. Subsequently, it is translated into viral polyproteins using host cell protein translation machinery, which are then cleaved into effector proteins by viral proteinases 3CLpro and PLpro.
The interaction between viral S protein and ACE2 on the host cell surface is of significant interest since it initiates the infection process. Researchers have been racing to find possible treatments to save lives and produce vaccines for future prevention.
To support research and development efforts to discover effective therapeutic and preventive agents for COVID, CAS, a division of the American Chemical Society specializing in scientific information solutions, has analyzed scientific data related to the development of therapeutic agents and vaccines for human coronaviruses since The analyses presented in this report are based on the CAS content collection, a scientist-curated data collection covering published scientific literature and patents from over 60 patent authorities worldwide.
Since the outbreak of COVID, this new disease and its causative virus have drawn major global attention. Scientists and physicians worldwide have been conducting a major campaign to understand this new emergent disease and its epidemiology in an effort to uncover possible treatment regimens, discover effective therapeutic agents, and develop vaccines. Over journal articles were published electronically or in print during this period, and the number of published articles has increased each week since the week of January 13, These trends reflect immense interest and desire from the scientific community, including both academic and industrial organizations as well as clinicians, to identify new methods to halt the progression of this epidemic disease and to prevent infection and transmission in the future.
Figure 4. Table 1 lists some journal articles published from December 30, through February 23, These articles were selected based on collective use of factors such as journal impact factor, citation, and type of study. For example, the No. Also shown in this table are journal articles pertaining to potential antiviral drug candidates such as remdesivir, baricitinib, and chloroquine for the treatment of this disease.
Table 1. This report identified pertinent data from patents related to these two coronaviruses. A similar distribution pattern was also observed for patents related to MERS.
Thus, for both diseases, more patents have been devoted to the development of therapeutic agents as opposed to diagnostic methods and vaccines. Table 2 lists potential targets, their roles in viral infection, and representative existing drugs or drug candidates that reportedly act on the corresponding targets in similar viruses and thus are to be assessed for their effects on SARS-CoV-2 infection.
Thus, drugs that target these proteases in other viruses such as HIV drugs, lopinavir and ritonavir, have been explored. For example, the broad-spectrum antiviral drug Arbidol, which functions as a virus-host cell fusion inhibitor to prevent viral entry into host cells against influenza virus, 20 has entered into a clinical trial for treatment of SARS-CoV Table 2.
ACE2 involvement with coronavirus infection is of further interest since ACE2 is a potent negative regulator restraining overactivation of the renin-angiotensin system RAS that may be involved in elicitation of inflammatory lung disease in addition to its well-known role in regulation of blood pressure and balance of body fluid and electrolytes.
The balance between angiotensin II and angiotensin 1—7 is critical since angiotensin II binds to angiotensin AT1 receptor to cause vasoconstriction, whereas angiotensin 1—7 elicits vasodilation mediated by AT2.
The CAS content collection contains patents related to coronavirus key proteins listed above. Table 3. An economic and efficient therapeutic strategy is to repurpose existing drugs. On the basis of genomic sequence information coupled with protein structure modeling, the scientific community has been able to rapidly respond with a suggested list of existing drugs with therapeutic potential for COVID Table 4 provides a summary of such drugs together with potential mechanisms of actions for their activities.
Barcitinib was proposed because of its anti-inflammatory effect and possible ability to reduce viral entry. Favipiravir, a purine nucleoside leading to inaccurate viral RNA synthesis, 36 was originally developed by Toyama Chemical of Japan, and has recently been approved for a clinical trial as a drug to treat COVID Table 4.
Table 5 shows selected patents associated with the aforementioned potential drugs, together with patents disclosing small molecules for treatment of SARS or MERS.
The selection was based on the presence of important terms in CAS-indexed patents as well as the presence of the synthetic preparation role assigned by CAS scientists during document indexing.
Patent applications WO and WO disclose preparation of compounds active as JAK inhibitors, one of which was later named as baricitinib and developed for reducing inflammation in rheumatoid arthritis. Patent application JP discloses preparation of polycyclic pyridone compounds and their use as endonuclease inhibitors. Patent applications US and US disclose preparation of the nucleotide analog drug remdesivir that was later developed as a therapeutic agent for Ebola and Marburg virus infections Patent US Table 5.
Patent application WO presents both preparation methods and biological assay results for compounds capable of inhibiting the SARS virus proteases. Drug administration routes were also mentioned in this patent. Besides various commercialized antiviral drugs, there are also small molecule compounds currently in research and development that have shown significant inhibitory effects on many key proteins from similar coronaviruses such as SARS-CoV and MERS-CoV Table 6.
These drug candidates mostly inhibit viral enzymes including proteases and components for RdRp. Since AT1 and AT2 are important effectors in the RAS system to which ACE2 belongs, it has been speculated that these compounds may be used to adjust the balance between AT1 and AT2, which may be affected by coronavirus infection and to alleviate viral-induced lung injury during the infection.
Table 6. Table 7 lists selected compounds that were also identified to have a pharmacological activity or therapeutic usage role.
Swagga Fresh Freddie, a Mixtape by Mouse on tha Track. Released 11 1 Intro. 2 Swagga Fresh Freddie. 3 Unwind. feat. Foxx & Shell. 4 Mad at Me. feat. Mouse on tha Track's Swagga Fresh Freddie is the ham; the it's free so I don't predict myself enjoying it, and when “Unwind” is, like, the best. Explore the largest community of artists, bands, podcasters and creators of music & audio. 03 - Unwind ft Shell Foxx. | Previous track Play or pause. Despite the horrible cover, Mouse On Tha Track's upcoming mixtape should have some good tracks on it. Download link after the jump! DOWNLOAD: Mouse On. Off of Mouse's upcoming tape. As usual this track is dope! Mouse On Tha Track Ft. Foxx & Shell – Unwind.
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