Embedded Files
Drug Discovery
Drug Discovery
Perspectives for Drug Discovery
Perspectives for Drug Discovery
Effective treatments must inhibit pathogenic actions by any foreign agent in the body. For example: every drug has a specific target that it must inhibit to further prevent pathogenesis and impairment. However, drug discovery is challenging as not one drug fits all; not one drug cures all diseases and viruses nor is one drug effective for everyone.
Pharmaceutical drugs are used to cure, treat, or prevent disease. They are classified based on their primary function, target (s), and impact on the body. Antivirals, immunomodulators, and antibiotics are all drug classes that each have specific functions in the body; (1) antivirals prevent the replication of viruses, (2) immunomodulators help regulate and normalize the immune system, and (3) antibiotics help treat bacterial infections like strep throat. These drug functions are universal. Meaning, one antiviral drug should ("theoretically") effectively treat all viral infections given that it targets the replication cycle of viruses. However, this is not the case because every virus has unique mechanisms by which it infects the host.
In conclusion, though drug discovery is complicated, it is essential for treating illnesses. To simplify drug discovery, scientists have to make several connections in biology. Specifically, they must study biological evolution to understand how such a simple "thing" became so complicated. Evolution is ongoing and life will continue to change and change, become more and more complex, and introduce things we have never seen. Therefore, attacking the complex changes in evolution may not be as valuable as diving deep into simplicity. Perhaps this simplicity is the foundation for finding cures to all diseases and viruses. After all, everything began somewhere; there must be something ancient (and simple) about every modernization and advancement in biology..... just my thought.....
Source: From NCBI, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725284/
Brief Perspective for COVID-19 Drug Discovery
Brief Perspective for COVID-19 Drug Discovery
The suggestions for Coronavirus drug discovery come from: (1) Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, Xu Y, Li M, Li X,Zheng M, Chen L, Li H, Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods, Acta Pharmaceutica Sinica B, https://doi.org/10.1016/j.apsb.2020.02.008, and (2) Nature Biotechnology. "Coronavirus puts drug repurposing on the fast track," https://www.nature.com/articles/d41587-020-00003-1.
General anti-Coronavirus treatment targets:
General anti-Coronavirus treatment targets:
The structure of SARS-CoV-2 is essential to understand in order to analyze various important drug targets on the virus. Some important targets to attack on COVID-19 are the 3-chymotrypsin-like protease (3CLpro), the Spike Protein, the RNA-dependent RNA polymerase (RdRp), the helicase, and the papain like protease (PLpro). These targets are all important in the viral entry and cleavage process. However, many other proteins on the viral surface of Coronaviruses play a role in facilitating viral entry and replication. Therefore, it is important to understand the genome structure of SARS-CoV-2 in order to develop effective drugs to target viral structures that enhance viral entry and replication. More genome structures for other viruses can be found here.
Most scientists are working on developing treatments that specifically target the Coronavirus in order inhibit viral entry, fusion, replication, as well as its other unique mechanisms to infect: (1) treatments can act on enzymes or functional proteins that are critical for viral replication and entry into the host cell, (2) treatments can also target structural proteins on the Coronavirus to completely block it from binding to cell membrane receptors, (3) treatments should target the 3CLpro and the papin-like protease to inhibit cleavage, and (4) treatments can inhibit viral RNA synthesis.
Anti-coronavirus treatments can also target the immune system given that it plays a major role in permitting viral entry and replication. An example of an immunoenhancer is interferon.
Human relative proteins like the ACE2 receptor and type-II transmembrane serine protease (TMPRSS2) enzymes are also possible targets. After all, SARS-CoV-2 uses the ACE2 receptor and the type-II transmembrane serine protease to enter host cells.
Above is the entire COVID-19 genome structure in correspondence to its physical viral structure. A more detailed caption can be found from ScienceDirect, https://www.sciencedirect.com/science/article/pii/S2211383520302999
Above is the genome structure of the COVID-19 Spike Protein. It is very important to understand the detailed genome structure of the virus because EVERY domain in the protein complex is important.
Image Credit: From Science, https://science.sciencemag.org/content/367/6483/1260
****MY THOUGHT:
****MY THOUGHT:
Instead of developing a treatment that targets the replication mechanisms of the Coronavirus, scientists can study the recognition mechanism of cell membrane receptors. Then, find a commonality among all receptors in order to develop a universal drug that block these receptors from accepting glycosylated viruses. Click here to see a table with viruses with their corresponding target receptor.
Potential Drug Treatments
Potential Drug Treatments
Ribavirin
Ribavirin
Ribavirin is an antiviral agent and a guanosine analog. Studies show that it can also be a Papin-like Protease Inhibitor.
Ribavirin is an antiviral agent and a guanosine analog. Studies show that it can also be a Papin-like Protease Inhibitor.
Self-Created table
Information from DrugBank, https://www.drugbank.ca/drugs/DB00811
Source: Embedded DrugBank
Valganciclovir
Valganciclovir
Valganciclovir is an antiviral agent and a prodrug for ganciclovir, which is an antiviral guanosine analog. Studies show that valganciclovir can also be a Papin-like Protease Inhibitor.
Valganciclovir is an antiviral agent and a prodrug for ganciclovir, which is an antiviral guanosine analog. Studies show that valganciclovir can also be a Papin-like Protease Inhibitor.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB00811
NCBI PubMed, https://www.ncbi.nlm.nih.gov/pubmed/11465875
Source: Embedded DrugBank
Aspartame
Aspartame
Aspartame is an artificial non-saccharide sweetener that can be used instead of sugar. Studies show that aspartame can also be a Papin-like Protease Inhibitor.
Aspartame is an artificial non-saccharide sweetener that can be used instead of sugar. Studies show that aspartame can also be a Papin-like Protease Inhibitor.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB00811
NCBI PubMed, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617129/
MedicalNewsToday, https://www.medicalnewstoday.com/articles/322266
Source: Embedded DrugBank
Remdesivir (developed by Gilead Sciences)
Remdesivir (developed by Gilead Sciences)
Remdesivir is an antiviral agent and an adenosine triphosphate analog.
Remdesivir is an antiviral agent and an adenosine triphosphate analog.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB00811
StatNews, https://www.statnews.com/pharmalot/2020/03/13/gilead-coronavirus-covid19-clinical-trials/
Source: Embedded DrugBank
Oseltamivir (Tamiflu)
Oseltamivir (Tamiflu)
Oseltamivir is an antiviral agent and a neuraminidase inhibitor.
Oseltamivir is an antiviral agent and a neuraminidase inhibitor.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB00811
Source: Embedded DrugBank
Umifenovir (Arbidol)
Umifenovir (Arbidol)
Umifenovir is an indole-based, hydrophobic, dual-acting direct antiviral and host-targeting agent.
Umifenovir is an indole-based, hydrophobic, dual-acting direct antiviral and host-targeting agent.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB00811
Source: Embedded DrugBank
Chloroquine
Chloroquine
Chloroquine is an aminoquinoline derivative (aminoquinoline: amino group is at 4th position of quinoline) and an antimalarial drug.
Chloroquine is an aminoquinoline derivative (aminoquinoline: amino group is at 4th position of quinoline) and an antimalarial drug.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB00811
CDC (Center for Disease Control), https://www.cdc.gov/malaria/resources/pdf/fsp/drugs/Chloroquine.pdf
Source: Embedded DrugBank
Hydroxychloroquine
Hydroxychloroquine
Hydroxychloroquine is an aminoquinoline derivative (aminoquinoline: amino group is at 4th position of quinoline), an antimalarial drug, and a racemic mixture consisting of an R and S enantiomer.
Hydroxychloroquine is an aminoquinoline derivative (aminoquinoline: amino group is at 4th position of quinoline), an antimalarial drug, and a racemic mixture consisting of an R and S enantiomer.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB01611
MedlinePlus, https://medlineplus.gov/druginfo/meds/a601240.html
Source: Embedded DrugBank
Baricitinib
Baricitinib
Baricitinib is a selective and reversible Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) inhibitor.
Baricitinib is a selective and reversible Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) inhibitor.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB00811
Versus Arthritis, https://www.versusarthritis.org/about-arthritis/treatments/drugs/baricitinib/
Source: Embedded DrugBank
Ivermectin
Ivermectin
Ivermectin is a broad-spectrum anti-parasite medication, also known as an an antihelmintic.
Ivermectin is a broad-spectrum anti-parasite medication, also known as an an antihelmintic.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB00811
WebMD, https://www.webmd.com/drugs/2/drug-1122/ivermectin-oral/details
Favipiravir (discovered by Toyama Chemical's in Tokyo, Japan)
Favipiravir (discovered by Toyama Chemical's in Tokyo, Japan)
Favipiravir is an antiviral pyrazine analog that targets RNA-dependant RNA Polymerase (RdRp) enzymes, which are crucial for viral replication.
Favipiravir is an antiviral pyrazine analog that targets RNA-dependant RNA Polymerase (RdRp) enzymes, which are crucial for viral replication.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB12466
Kaletra: Lopinavir + Ritonavir
Kaletra: Lopinavir + Ritonavir
Developed by AbbVie Company
Developed by AbbVie Company
Lopinavir
Lopinavir
Lopinavir is an antiretroviral protease inhibitor used to treat HIV-1 infections when combined with other antiretrovirals like ritonavir. Lopinavir's efficacy is significantly lower when it is used as an individual drug. When high doses of lopinavir are used in combination with a "booster" drug like ritonavir, its antiviral activity improves
Lopinavir is an antiretroviral protease inhibitor used to treat HIV-1 infections when combined with other antiretrovirals like ritonavir. Lopinavir's efficacy is significantly lower when it is used as an individual drug. When high doses of lopinavir are used in combination with a "booster" drug like ritonavir, its antiviral activity improves
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB01601
MedlinePlus, https://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?v%3Aproject=medlineplus&v%3Asources=medlineplus-bundle&query=lopinavir&_ga=2.179484711.229990798.1586624659-1664915242.1560984708
Ritonavir
Ritonavir
Ritonavir is an antiviral HIV protease inhibitor that inhibits the proper reproduction of the virus. This drug works most efficiently when low doses of it are combined with other protease inhibitors like lopinavir. It is therefore a "booster" drug, improving the antiviral activity of other protease inhibitors.
Ritonavir is an antiviral HIV protease inhibitor that inhibits the proper reproduction of the virus. This drug works most efficiently when low doses of it are combined with other protease inhibitors like lopinavir. It is therefore a "booster" drug, improving the antiviral activity of other protease inhibitors.
Self-Created table
Information from
DrugBank, https://www.drugbank.ca/drugs/DB00503
MedlinePlus, https://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?v%3Aproject=medlineplus&v%3Asources=medlineplus-bundle&query=lopinavir&_ga=2.179484711.229990798.1586624659-1664915242.1560984708
Prezcobix: Darunavir + Cobicistat
Prezcobix: Darunavir + Cobicistat
Page updated
Google Sites
Report abuse