Protease Inhibitors from Plants as Therapeutic Agents- A Review

2022 ◽  
Author(s):  
M. S. Cid-Gallegos ◽  
L. J. Corzo-Ríos ◽  
C. Jiménez-Martínez ◽  
X. M. Sánchez-Chino
Keyword(s):  
Protease Inhibitors ◽  
Therapeutic Agents

scholarly journals MK-5172, a Selective Inhibitor of Hepatitis C Virus NS3/4a Protease with Broad Activity across Genotypes and Resistant Variants

2012 ◽  
Vol 56 (8) ◽  
pp. 4161-4167 ◽  
Author(s):  
Vincenzo Summa ◽  
Steven W. Ludmerer ◽  
John A. McCauley ◽  
Christine Fandozzi ◽  
Christine Burlein ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Selective Pressure ◽  
Pegylated Interferon ◽  
Therapeutic Agents ◽  
Hepatitis C Virus Infection ◽  
Dosing Regimen ◽  
Once Daily ◽  
Hcv Genotypes

ABSTRACTHCV NS3/4a protease inhibitors are proven therapeutic agents against chronic hepatitis C virus infection, with boceprevir and telaprevir having recently received regulatory approval as add-on therapy to pegylated interferon/ribavirin for patients harboring genotype 1 infections. Overcoming antiviral resistance, broad genotype coverage, and a convenient dosing regimen are important attributes for future agents to be used in combinations without interferon. In this communication, we report the preclinical profile of MK-5172, a novel P2-P4 quinoxaline macrocyclic NS3/4a protease inhibitor currently in clinical development. The compound demonstrates subnanomolar activity against a broad enzyme panel encompassing major hepatitis C virus (HCV) genotypes as well as variants resistant to earlier protease inhibitors. In replicon selections, MK-5172 exerted high selective pressure, which yielded few resistant colonies. In both rat and dog, MK-5172 demonstrates good plasma and liver exposures, with 24-h liver levels suggestive of once-daily dosing. When administered to HCV-infected chimpanzees harboring chronic gt1a or gt1b infections, MK-5172 suppressed viral load between 4 to 5 logs at a dose of 1 mg/kg of body weight twice daily (b.i.d.) for 7 days. Based on its preclinical profile, MK-5172 is anticipated to be broadly active against multiple HCV genotypes and clinically important resistance variants and highly suited for incorporation into newer all-oral regimens.

scholarly journals A Review on Therapeutic Potential of Protease Inhibitors from Medicinal Plants

2019 ◽  
pp. 1-11
Author(s):  
R. N. N. Gamage ◽  
K. D. K. P. Kumari
Keyword(s):  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Blood Clotting ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Geographical Location ◽  
Therapeutic Agents ◽  
Human Diseases ◽  
Plant Protease ◽  
Protease Specificity

Most of the currently available therapeutic agents, particularly for cardiovascular disorders and cancers are very expensive and induce some serious side effects. Some of these drugs have also become less effective due to the emergence of antibiotic resistance. There is a necessity and great demand for the development of novel efficacious plant-based agents that are of pharmacologically effective. In this connection, this review focuses on therapeutic potential of plant protease inhibitors. Protease inhibitors are of a particular concern at present due to their potent ability to inhibit protease enzymes that are involved in pathogenesis of various human diseases. In addition to their function as protein-degrading enzymes, protease inhibitors are now well-known for their capability to involve in many biological activities as signaling molecules. Plant protease inhibitors are also engaged in several physiological and pathological processes, such as blood clotting, inflammation, immune regulation, apoptosis and carcinogenesis. Therefore, isolation of plant protease inhibitors and evaluation of their therapeutic capacity against chronic human diseases have become a major research interest. Nevertheless, protease inhibitor content and protease specificity vary significantly even in the same plant species depending on the geographical location and environmental factors. Consequently, it is important to identify potent therapeutic potential of each plant protease inhibitor on human health individually.

Recent development of 3C and 3CL protease inhibitors for anti-coronavirus and anti-picornavirus drug discovery

2011 ◽  
Vol 39 (5) ◽  
pp. 1371-1375 ◽  
Author(s):  
R. Ramajayam ◽  
Kian-Pin Tan ◽  
Po-Huang Liang
Keyword(s):  
Drug Discovery ◽  
Severe Acute Respiratory Syndrome ◽  
Protease Inhibitors ◽  
Therapeutic Agents ◽  
3C Protease ◽  
The World ◽  
Structural Differences ◽  
Life Threatening ◽  
Dual Inhibitors ◽  
3Cl Protease

SARS-CoV (severe acute respiratory syndrome-associated coronavirus) caused infection of ~8000 people and death of ~800 patients around the world during the 2003 outbreak. In addition, picornaviruses such as enterovirus, coxsackievirus and rhinovirus also can cause life-threatening diseases. Replication of picornaviruses and coronaviruses requires 3Cpro (3C protease) and 3CLpro (3C-like protease) respectively, which are structurally analogous with chymotrypsin-fold, but the former is a monomer and the latter is dimeric due to an extra third domain for dimerization. Subtle structural differences in the S2 and S3 pockets of these proteases make inhibitors selective, but some dual inhibitors have been discovered. Our findings as summarized in the present review provide new potential anti-coronavirus and anti-picornavirus therapeutic agents and a clue to convert 3CLpro inhibitors into 3Cpro inhibitors and vice versa.

scholarly journals Natural Bioactive Compounds from Fungi as Potential Candidates for Protease Inhibitors and Immunomodulators to Apply for Coronaviruses

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1800 ◽  
Author(s):  
Nakarin Suwannarach ◽  
Jaturong Kumla ◽  
Kanaporn Sujarit ◽  
Thanawat Pattananandecha ◽  
Chalermpong Saenjum ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Bioactive Compounds ◽  
Therapeutic Potential ◽  
Antiviral Drug ◽  
Therapeutic Agents ◽  
Viral Protease ◽  
Drug Discovery And Development ◽  
Adverse Side Effects ◽  
Important Target ◽  
Hiv 1

The inhibition of viral protease is an important target in antiviral drug discovery and development. To date, protease inhibitor drugs, especially HIV-1 protease inhibitors, have been available for human clinical use in the treatment of coronaviruses. However, these drugs can have adverse side effects and they can become ineffective due to eventual drug resistance. Thus, the search for natural bioactive compounds that were obtained from bio-resources that exert inhibitory capabilities against HIV-1 protease activity is of great interest. Fungi are a source of natural bioactive compounds that offer therapeutic potential in the prevention of viral diseases and for the improvement of human immunomodulation. Here, we made a brief review of the current findings on fungi as producers of protease inhibitors and studies on the relevant candidate fungal bioactive compounds that can offer immunomodulatory activities as potential therapeutic agents of coronaviruses in the future.

Biologic protease inhibitors as novel therapeutic agents

Biochimie ◽  
2010 ◽  
Vol 92 (11) ◽  
pp. 1681-1688 ◽  
Author(s):  
Christopher J. Scott ◽  
Clifford C. Taggart
Keyword(s):  
Protease Inhibitors ◽  
Therapeutic Agents ◽  
Novel Therapeutic

scholarly journals Potential therapeutic target identification in the novel 2019 coronavirus: insight from homology modeling and blind docking study

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Olanrewaju Ayodeji Durojaye ◽  
Talifhani Mushiana ◽  
Henrietta Onyinye Uzoeto ◽  
Samuel Cosmas ◽  
Victor Malachy Udowo ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Target Identification ◽  
Rna Virus ◽  
3D Structure ◽  
Docking Study ◽  
Therapeutic Agents ◽  
Proteolytic Processing ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Novel Coronavirus

Abstract Background The 2019-nCoV which is regarded as a novel coronavirus is a positive-sense single-stranded RNA virus. It is infectious to humans and is the cause of the ongoing coronavirus outbreak which has elicited an emergency in public health and a call for immediate international concern has been linked to it. The coronavirus main proteinase which is also known as the 3C-like protease (3CLpro) is a very important protein in all coronaviruses for the role it plays in the replication of the virus and the proteolytic processing of the viral polyproteins. The resultant cytotoxic effect which is a product of consistent viral replication and proteolytic processing of polyproteins can be greatly reduced through the inhibition of the viral main proteinase activities. This makes the 3C-like protease of the coronavirus a potential and promising target for therapeutic agents against the viral infection. Results This study describes the detailed computational process by which the 2019-nCoV main proteinase coding sequence was mapped out from the viral full genome, translated and the resultant amino acid sequence used in modeling the protein 3D structure. Comparative physiochemical studies were carried out on the resultant target protein and its template while selected HIV protease inhibitors were docked against the protein binding sites which contained no co-crystallized ligand. Conclusion In line with results from this study which has shown great consistency with other scientific findings on coronaviruses, we recommend the administration of the selected HIV protease inhibitors as first-line therapeutic agents for the treatment of the current coronavirus epidemic.

SEM of non-coated hepatocellular cytoskeleton of perfused livers

1984 ◽  
Vol 42 ◽  
pp. 306-307
Author(s):  
S.W. French ◽  
N.C. Benson ◽  
C. Davis-Scibienski
Keyword(s):  
Ambient Temperature ◽  
Critical Point ◽  
Protease Inhibitors ◽  
Metal Deposition ◽  
Heat Damage ◽  
Detergent Extraction ◽  
Cytoskeletal Elements ◽  
Triton X ◽  
Excised Tissue

Previous SEM studies of liver cytoskeletal elements have encountered technical difficulties such as variable metal coating and heat damage which occurs during metal deposition. The majority of studies involving evaluation of the cell cytoskeleton have been limited to cells which could be isolated, maintained in culture as a monolayer and thus easily extracted. Detergent extraction of excised tissue by immersion has often been unsatisfactory beyond the depth of several cells. These disadvantages have been avoided in the present study. Whole C3H mouse livers were perfused in situ with 0.5% Triton X-100 in a modified Jahn's buffer including protease inhibitors. Perfusion was continued for 1 to 2 hours at ambient temperature. The liver was then perfused with a 2% buffered gluteraldehyde solution. Liver samples including spontaneous tumors were then maintained in buffered gluteraldehyde for 2 hours. Samples were processed for SEM and TEM using the modified thicarbohydrazide procedure of Malich and Wilson, cryofractured, and critical point dried (CPD). Some samples were mechanically fractured after CPD.

Water-soluble amphiphilic ruthenium(ii) polypyridyl complexes as potential light-activated therapeutic agents

2020 ◽  
Vol 56 (65) ◽  
pp. 9332-9335
Author(s):  
Sandra Estalayo-Adrián ◽  
Salvador Blasco ◽  
Sandra A. Bright ◽  
Gavin J. McManus ◽  
Guillermo Orellana ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Therapeutic Agents ◽  
Water Soluble ◽  
Polypyridyl Complexes ◽  
Cervical Cancer Cells

Two new water-soluble amphiphilic Ru(ii) polypyridyl complexes were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and phototoxicity against HeLa cervical cancer cells.

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