scholarly journals Impact of Natural Products on Developing New Treatments for Corona Virus Disease (COVID-19): Review

2021 ◽  
pp. 101-122
Author(s):  
Amna A. Saddiq ◽  
Enas N. Danial ◽  
Iman A. Saraf
Keyword(s):  
Natural Products ◽  
Drug Development ◽  
Viral Replication ◽  
Virus Disease ◽  
Viral Proteins ◽  
Antiviral Action ◽  
Normal Mixtures ◽  
Speed Up ◽  
Reduce Risk ◽  
New Treatments

COVID-19 is dominatingly considered as an unavoidable pandemic, and researchers are exceptionally inquisitive about how to give the best assurance to people in general before an immunization can be made accessible. Normal items have consistently assumed an essential part in drug advancement measure against different illnesses, which brought about screening of such specialists to battle emanant freaks of infections. Contingent upon the construction, component of activity and hazard elements of Covid-19, this audit centers around those normal mixtures that showed promising outcomes against Corona infections. Although restraint of viral replication is frequently considered as an overall component for antiviral action of many of the characteristic items, contemplates have shown that some regular items can connect with key viral proteins that are related with destructiveness. Supplementation of natural products might be a affect to reduce risk through different mechanisms. In this unique circumstance, a portion of the regular items have antiviral action in the nanomolar fixation and could be leads for additional medication advancement all alone or as a format for drug plan. Also, a decent number of normal items with against Covid action are the significant constituents of some regular dietary enhancements, which can be abused to improve the resistance of everyone in specific scourges The candidate compounds identified by us may help to speed up the drug development against COVID-19.

Possible Targets and Therapies of SARS-CoV-2 Infection

2020 ◽  
Vol 20 (18) ◽  
pp. 1900-1907
Author(s):  
Kasturi Sarkar ◽  
Parames C. Sil ◽  
Seyed Fazel Nabavi ◽  
Ioana Berindan-Neagoe ◽  
Cosmin Andrei Cismaru ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Viral Infection ◽  
Human Activity ◽  
Viral Proteins ◽  
Therapeutic Agents ◽  
Effective Control ◽  
Human Society ◽  
Global Spread ◽  
Repurposed Drugs

The global spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes COVID-19 has become a source of grave medical and socioeconomic concern to human society. Since its first appearance in the Wuhan region of China in December 2019, the most effective measures of managing the spread of SARS-CoV-2 infection have been social distancing and lockdown of human activity; the level of which has not been seen in our generations. Effective control of the viral infection and COVID-19 will ultimately depend on the development of either a vaccine or therapeutic agents. This article highlights the progresses made so far in these strategies by assessing key targets associated with the viral replication cycle. The key viral proteins and enzymes that could be targeted by new and repurposed drugs are discussed.

scholarly journals Renal Manifestations of Covid-19: Physiology and Pathophysiology

2021 ◽  
Vol 10 (6) ◽  
pp. 1216
Author(s):  
Zaher Armaly ◽  
Safa Kinaneh ◽  
Karl Skorecki
Keyword(s):  
Viral Replication ◽  
Virus Disease ◽  
Multiorgan Failure ◽  
Critical Role ◽  
Kidney Injury ◽  
Small Sample ◽  
Renal Physiology ◽  
High Morbidity ◽  
Enzymatic Production ◽  
High Incidence

Corona virus disease 2019 (COVID-19) imposes a serious public health pandemic affecting the whole world, as it is spreading exponentially. Besides its high infectivity, SARS-CoV-2 causes multiple serious derangements, where the most prominent is severe acute respiratory syndrome as well as multiple organ dysfunction including heart and kidney injury. While the deleterious impact of SARS-CoV-2 on pulmonary and cardiac systems have attracted remarkable attention, the adverse effects of this virus on the renal system is still underestimated. Kidney susceptibility to SARS-CoV-2 infection is determined by the presence of angiotensin-converting enzyme 2 (ACE2) receptor which is used as port of the viral entry into targeted cells, tissue tropism, pathogenicity and subsequent viral replication. The SARS-CoV-2 cellular entry receptor, ACE2, is widely expressed in proximal epithelial cells, vascular endothelial and smooth muscle cells and podocytes, where it supports kidney integrity and function via the enzymatic production of Angiotensin 1-7 (Ang 1-7), which exerts vasodilatory, anti-inflammatory, antifibrotic and diuretic/natriuretic actions via activation of the Mas receptor axis. Loss of this activity constitutes the potential basis for the renal damage that occurs in COVID-19 patients. Indeed, several studies in a small sample of COVID-19 patients revealed relatively high incidence of acute kidney injury (AKI) among them. Although SARS-CoV-1 -induced AKI was attributed to multiorgan failure and cytokine release syndrome, as the virus was not detectable in the renal tissue of infected patients, SARS-CoV-2 antigens were detected in kidney tubules, suggesting that SARS-CoV-2 infects the human kidney directly, and eventually induces AKI characterized with high morbidity and mortality. The mechanisms underlying this phenomenon are largely unknown. However, the fact that ACE2 plays a crucial role against renal injury, the deprivation of the kidney of this advantageous enzyme, along with local viral replication, probably plays a central role. The current review focuses on the critical role of ACE2 in renal physiology, its involvement in the development of kidney injury during SARS-CoV-2 infection, renal manifestations and therapeutic options. The latter includes exogenous administration of Ang (1-7) as an appealing option, given the high incidence of AKI in this ACE2-depleted disorder, and the benefits of ACE2/Ang1-7 including vasodilation, diuresis, natriuresis, attenuation of inflammation, oxidative stress, cell proliferation, apoptosis and coagulation.

scholarly journals Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: A review

2015 ◽  
Vol 6 (1) ◽  
pp. 17-33 ◽  
Author(s):  
Mohamed-Elamir F. Hegazy ◽  
Tarik A. Mohamed ◽  
Abdelsamed I. ElShamy ◽  
Abou-El-Hamd H. Mohamed ◽  
Usama A. Mahalel ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Development ◽  
Mevalonic Acid ◽  
Mevalonic Acid Pathway ◽  
Acid Pathway

scholarly journals Network-Guided Discovery of Influenza Virus Replication Host Factors

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Emily E. Ackerman ◽  
Eiryo Kawakami ◽  
Manami Katoh ◽  
Tokiko Watanabe ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Replication ◽  
Virus Replication ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Viral Proteins ◽  
Host Factors ◽  
Ppi Network ◽  
Host Proteins ◽  
Influenza Virus Replication

ABSTRACTThe positions of host factors required for viral replication within a human protein-protein interaction (PPI) network can be exploited to identify drug targets that are robust to drug-mediated selective pressure. Host factors can physically interact with viral proteins, be a component of virus-regulated pathways (where proteins do not interact with viral proteins), or be required for viral replication but unregulated by viruses. Here, we demonstrate a method of combining human PPI networks with virus-host PPI data to improve antiviral drug discovery for influenza viruses by identifying target host proteins. Analysis shows that influenza virus proteins physically interact with host proteins in network positions significant for information flow, even after the removal of known abundance-degree bias within PPI data. We have isolated a subnetwork of the human PPI network that connects virus-interacting host proteins to host factors that are important for influenza virus replication without physically interacting with viral proteins. The subnetwork is enriched for signaling and immune processes distinct from those associated with virus-interacting proteins. Selecting proteins based on subnetwork topology, we performed an siRNA screen to determine whether the subnetwork was enriched for virus replication host factors and whether network position within the subnetwork offers an advantage in prioritization of drug targets to control influenza virus replication. We found that the subnetwork is highly enriched for target host proteins—more so than the set of host factors that physically interact with viral proteins. Our findings demonstrate that network positions are a powerful predictor to guide antiviral drug candidate prioritization.IMPORTANCEIntegrating virus-host interactions with host protein-protein interactions, we have created a method using these established network practices to identify host factors (i.e., proteins) that are likely candidates for antiviral drug targeting. We demonstrate that interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza virus replication are enriched for signaling and immune processes. Additionally, we show that host proteins that interact with viral proteins are in network locations of power. Finally, we demonstrate a new network methodology to predict novel host factors and validate predictions with an siRNA screen. Our results show that integrating virus-host proteins interactions is useful in the identification of antiviral drug target candidates.

scholarly journals Identification of Diaryl-Quinoline Compounds as Entry Inhibitors of Ebola Virus

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 678 ◽  
Author(s):  
Qinghua Cui ◽  
Han Cheng ◽  
Rui Xiong ◽  
Gang Zhang ◽  
Ruikun Du ◽  
...  
Keyword(s):  
Drug Development ◽  
Ebola Virus ◽  
Virus Disease ◽  
Virus Entry ◽  
Surface Protein ◽  
Host Cells ◽  
Entry Inhibitor ◽  
Entry Inhibitors ◽  
Promising Target ◽  
Virus Entry Inhibitors

Ebola virus is the causative agent of Ebola virus disease in humans. The lethality of Ebola virus infection is about 50%, supporting the urgent need to develop anti-Ebola drugs. Glycoprotein (GP) is the only surface protein of the Ebola virus, which is functionally critical for the virus to attach and enter the host cells, and is a promising target for anti-Ebola virus drug development. In this study, using the recombinant HIV-1/Ebola pseudovirus platform we previously established, we evaluated a small molecule library containing various quinoline compounds for anti-Ebola virus entry inhibitors. Some of the quinoline compounds specifically inhibited the entry of the Ebola virus. Among them, compound SYL1712 was the most potent Ebola virus entry inhibitor with an IC50 of ~1 μM. The binding of SYL1712 to the vial glycoprotein was computationally modeled and was predicted to interact with specific residues of GP. We used the time of the addition assay to show that compound SYL1712 blocks Ebola GP-mediated entry. Finally, consistent with being an Ebola virus entry inhibitor, compound SYL1712 inhibited infectious Ebola virus replication in tissue culture under biosafety level 4 containment, with an IC50 of 2 μM. In conclusion, we identified several related molecules with a diaryl-quinoline scaffold as potential anti-EBOV entry inhibitors, which can be further optimized for anti-Ebola drug development.

scholarly journals Synergistic effects of natural products and commercial antibiotics

2020 ◽  
Author(s):  
Lucia Nitsch-Velasquez
Keyword(s):  
Natural Products ◽  
Synergistic Effects ◽  
Gram Negative Bacteria ◽  
Polar Solvents ◽  
Microbial Strains ◽  
Polar Extracts ◽  
Review Reports ◽  
New Treatments ◽  
Discovery Pipeline

Context: The antimicrobial resistant era requires advances in the approaches and technologies to find new treatments. The enhancement of the antimicrobial activity of commercially available drugs (CADs) by natural products (NPs) has successful mixtures (e.g., clavulanic acid and amoxicillin). Objective: To systematically review reports of synergistic effects of CADs and NPs against opportunistic microbial strains from 2010 to April 2016. Methods: The databases and search engines PubMed, Medline, Scifinder, Scopus, ScienceDirect, Scholar Google were systematically searched. Among the keywords utilized were: synergistic effects natural products and antibioitcs, botanicals and antibiotics bioassays, plant extracts interaction with antibioitics and antibiotic adjuvant bioassays. Only synergistic results were tabulated and analyzed according to CADs, NPs and strains. Results: A set of 76 studies that reported in vitro synergistic effects of CADs and NPs against gram−positive or gram−negative bacteria or fungi opportunistic strains was found. From the 60 reports on antibacterial adjuvants, the most frequent designs involved beta−lactamics or aminoglycosides against Methicillin Resistant Staphylococcus aureus. The assayed NPs encompassed extracts or fractions from 22 different species distributed worldwide (45% extracted with non−polar solvents) and 33 purified compounds (flavonoids, other polyphenols and alkaloids). Conclusions: NPs as potential drug hits for antimicrobial adjuvants had been found and should continue in the drug discovery pipeline. The field certainly would benefit of advances in purification technologies, especially for polar extracts and bioassay platforms.

scholarly journals Insights into Ebola Virus VP35 and VP24 Interferon Inhibitory Functions and their Initial Exploitation as Drug Targets

2019 ◽  
Vol 19 (4) ◽  
pp. 362-374 ◽  
Author(s):  
Elisa Fanunza ◽  
Aldo Frau ◽  
Angela Corona ◽  
Enzo Tramontano
Keyword(s):  
Drug Development ◽  
Drug Targets ◽  
Cellular Response ◽  
Ebola Virus ◽  
Virus Disease ◽  
Structural Characteristics ◽  
Inhibitory Function ◽  
The Family ◽  
Effective Shield ◽  
Cellular Immune

Upon viral infection, the interferon (IFN) system triggers potent antiviral mechanisms limiting viral growth and spread. Hence, to sustain their infection, viruses evolved efficient counteracting strategies to evade IFN control. Ebola virus (EBOV), member of the family Filoviridae, is one of the most virulent and deadly pathogen ever faced by humans. The etiological agent of the Ebola Virus Disease (EVD), EBOV can be undoubtedly considered the perfect example of a powerful inhibitor of the host organism immune response activation. Particularly, the efficacious suppression of the IFN cascade contributes to disease progression and severity. Among the EBOVencoded proteins, the Viral Proteins 35 (VP35) and 24 (VP24) are responsible for the EBOV extreme virulence, representing the core of such inhibitory function through which EBOV determines its very effective shield to the cellular immune defenses. VP35 inhibits the activation of the cascade leading to IFN production, while VP24 inhibits the activation of the IFN-stimulated genes. A number of studies demonstrated that both VP35 and VP24 is validated target for drug development. Insights into the structural characteristics of VP35 and VP24 domains revealed crucial pockets exploitable for drug development. Considered the lack of therapy for EVD, restoring the immune activation is a promising approach for drug development. In the present review, we summarize the importance of VP35 and VP24 proteins in counteracting the host IFN cellular response and discuss their potential as druggable viral targets as a promising approach toward attenuation of EBOV virulence.

Potential Phytochemical Nanoemulsions in the Treatment of Oral Cancer and Oral Health

2022 ◽  
pp. 330-353
Author(s):  
Dharmeswar Barhoi ◽  
Sweety Nath Barbhuiya ◽  
Sarbani Giri
Keyword(s):  
Natural Products ◽  
Radiation Therapy ◽  
Oral Health ◽  
Side Effects ◽  
Oral Cancer ◽  
Medicinal Plants ◽  
Drug Development ◽  
Health Management ◽  
Free Form ◽  
New Drug Development

Oral cancer is one of the most common types of cancer, and lifestyle factors like extensive consumption of tobacco, betel quid, and alcohol are the major etiological factors of oral cancer. Treatment of oral cancer includes surgery, radiation therapy, and chemotherapy, but this treatment possesses lots of side effects. Therefore, scientists and medical experts are utilizing natural products and medicinal plants for new drug development. Natural products and phytochemicals showed better efficacy with less toxicity. However, most of the phytochemicals showed poor permeability and less bioavailability. To combat this problem, scientists developed nanosized nanoemulsions of phytochemicals to treat various ailments. Nanoemulsions of phytochemicals exhibited better efficacy than their free form due to increased permeability and bioavailability. Numerous phytopharmaceuticals have been formulated for nanoemulsions to date and tested for their anticancer potential against various cancers, including oral cancer and oral health management.

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