Identification of C5-NH2 Modified Oseltamivir Derivatives as Novel Influenza Neuraminidase Inhibitors with Highly Improved Antiviral Activities and Favorable Druggability

Background: Novel Corona virus is a type of enveloped viruses with a single stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. Objective: We had selected 30 phytoconstituents from the different plants which are reported for antiviral activities against corona virus (CoVs) and performed insilico screening to find out phytoconstituents which have potency to inhibit specific target of novel corona virus. Methods: We had perform molecular docking studies on three different proteins of novel corona virus namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. Results: We had screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin using insilico approach. All compounds found safe in insilico toxicity studies. Bioactivity prediction reviles that these all compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had higher binding affinity for the target PLpro and Spike protein. Conclusion: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

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Carbohydrate-Binding Agents: Potential of Repurposing for COVID-19 Therapy

Current Protein and Peptide Science ◽

10.2174/1389203721666200918153717 ◽

2020 ◽

Vol 21 (11) ◽

pp. 1085-1096 ◽

Cited By ~ 2

Author(s):

Rajesh Kumar Gupta ◽

Girish R. Apte ◽

Kiran Bharat Lokhande ◽

Satyendra Mishra ◽

Jayanta K. Pal

Keyword(s):

Vaccine Development ◽

Host Cells ◽

Carbohydrate Binding ◽

Atypical Pneumonia ◽

The Novel ◽

High Infection ◽

Binding Agents ◽

Current Scenario ◽

Antiviral Activities ◽

Novel Drug

: With the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the whole world is suffering from atypical pneumonia, which resulted in more than 559,047 deaths worldwide. In this time of crisis and urgency, the only hope comes from new candidate vaccines and potential antivirals. However, formulating new vaccines and synthesizing new antivirals are a laborious task. Therefore, considering the high infection rate and mortality due to COVID-19, utilization of previous information, and repurposing of existing drugs against valid viral targets have emerged as a novel drug discovery approach in this challenging time. The transmembrane spike (S) glycoprotein of coronaviruses (CoVs), which facilitates the virus’s entry into the host cells, exists in a homotrimeric form and is covered with N-linked glycans. S glycoprotein is known as the main target of antibodies having neutralizing potency and is also considered as an attractive target for therapeutic or vaccine development. Similarly, targeting of N-linked glycans of S glycoprotein envelope of CoV via carbohydrate-binding agents (CBAs) could serve as an attractive therapeutic approach for developing novel antivirals. CBAs from natural sources like lectins from plants, marine algae and prokaryotes and lectin mimics like Pradimicin-A (PRM-A) have shown antiviral activities against CoV and other enveloped viruses. However, the potential use of CBAs specifically lectins was limited due to unfavorable responses like immunogenicity, mitogenicity, hemagglutination, inflammatory activity, cellular toxicity, etc. Here, we reviewed the current scenario of CBAs as antivirals against CoVs, presented strategies to improve the efficacy of CBAs against CoVs; and studied the molecular interactions between CBAs (lectins and PRM-A) with Man9 by molecular docking for potential repurposing against CoVs in general, and SARSCoV- 2, in particular.

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Potentials of Diphenyl Ether Scaffold as a Therapeutic Agent: A Review

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190312150132 ◽

2019 ◽

Vol 19 (17) ◽

pp. 1392-1406

Author(s):

Suvarna G. Kini ◽

Ekta Rathi ◽

Avinash Kumar ◽

Varadaraj Bhat

Keyword(s):

Therapeutic Agent ◽

Diphenyl Ether ◽

Biological Properties ◽

Industrial Applications ◽

Synthetic Route ◽

Structure Activity ◽

Diphenyl Ethers ◽

Antiviral Activities ◽

Synthetic Routes ◽

The 19Th Century

Diphenyl ethers (DPE) and its analogs have exhibited excellent potential for therapeutic and industrial applications. Since the 19th century, intensive research is perpetuating on the synthetic routes and biological properties of DPEs. Few well-known DPEs are Nimesulide, Fenclofenac, Triclosan, Sorafenib, MK-4965, and MK-1439 which have shown the potential of this moiety as a lead scaffold for different pharmacological properties. In this review, we recapitulate the diverse synthetic route of DPE moiety inclusive of merits and demerits over the classical synthetic route and how this moiety sparked an interest in researchers to discern the SAR (Structure Activity Relationship) for the development of diversified biological properties of DPEs such as antimicrobial, antifungal, antiinflammatory & antiviral activities.

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Punica granatum as a Source of Natural Antioxidant and Antimicrobial Agent; a Comprehensive Review on Related Investigations

Current Drug Discovery Technologies ◽

10.2174/1570163817666200430001822 ◽

2020 ◽

Vol 17 ◽

Author(s):

Atefeh Jalali ◽

Mohammadreza Kiafar ◽

Masih Seddigh ◽

Mohammad M. Zarshenas

Keyword(s):

Antioxidant Activities ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Natural Antioxidants ◽

Punica Granatum ◽

Antimicrobial Activities ◽

Natural Antioxidant ◽

Antiviral Activities ◽

Natural Foods

Background: The consumption of natural antioxidants is increasing due to the demand and tendency to natural foods. Punica granatum L. [Punicaceae] is a fruit with various bioactive ingredients. The effectiveness of this plant has been proved against various disorders such as hyperglycemia, hyperlipidemia, blood coagulation, infections, cancer, and dentistry. Among them, there are numerous researches on antimicrobial and antioxidant properties. Subsequently, the present study aimed to compile a review of those properties to outline this herb as a possible natural antioxidant and preservative. Methods: Synchronically, keywords "Punica granatum" with antimicrobial, or antibacterial, antifungal, antiviral, antioxidant and radical scavenging were searched through "Scopus" database up to 31st September 2019. Papers focusing on agriculture, genetics, chemistry, and environmental sciences were excluded and also related papers were collected. Results: Among 201 papers focusing on related activities, 111 papers have dealt with antioxidant activities focusing based on DPPH assay, 59 with antibacterial, on both gram+ and gram- bacteria, 24 with antifungal effects, mostly on Aspergillus niger and Candida albicans, and 7 papers with antiviral activities. There were about 50 papers focusing on in-vivo antioxidant activities of this plant. Conclusion: Taken together, botanical parts of P. granatum have possessed notable radical scavenging and antimicrobial activities that with these properties, this plant can be introduced as a natural safe source of preservative and antioxidant. Accordingly, P. granatum can be applied as excipient with the aforementioned properties in the pharmaceutical and food industries.

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New 2-Oxopyridine/2-Thiopyridine Derivatives Tethered to a Benzotriazole with Cytotoxicity on MCF7 Cell Lines and with Antiviral Activities

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190220123547 ◽

2020 ◽

Vol 17 (2) ◽

pp. 124-137 ◽

Cited By ~ 2

Author(s):

Adel Mahmoud Attia ◽

Ahmed Ibrahin Khodair ◽

Eman Abdelnasser Gendy ◽

Mohammed Abu El-Magd ◽

Yaseen Ali Mosa Mohamed Elshaier

Keyword(s):

Dna Damage ◽

Anticancer Agents ◽

Active Compound ◽

Docking Study ◽

Base Pairs ◽

Dna Base ◽

Dna Base Pairs ◽

Antiviral Activities ◽

Active Methylene ◽

Damage Study

Background:Perturbation of nucleic acids structures and confirmation by small molecules through intercalation binding is an intriguing application in anticancer therapy. The planar aromatic moiety of anticancer agents was inserted between DNA base pairs leading to change in the DNA structure and subsequent functional arrest.Objective:The final scaffold of the target compounds was annulated and linked to a benzotriazole ring. These new pharmacophoric features were examined as antiviral and anticancer agents against MCF7 and their effect on DNA damage was also assessed.Methods:A new series of fully substituted 2-oxopyridine/2-thioxopyridine derivatives tethered to a benzotriazole moiety (4a-h) was synthesized through Michael cyclization of synthesized α,β- unsaturated compounds (3a-e) with appropriate active methylene derivatives. The DNA damage study was assessed by comet assay. In silico DNA molecular docking was performed using Open Eye software to corroborate the experimental results and to understand molecule interaction at the atomic level.Results:The highest DNA damage was observed in Doxorubicin, followed by 4h, then, 4b, 4g, 4f, 4e, and 4d. The docking study showed that compound 4h formed Hydrogen Bonds (HBs) as a standard ligand with GSK-3. Compound 4h was the most active compound against rotavirus Wa, HAVHM175, and HSV strains with a reduction of 30%, 40%, and 70%, respectively.Conclusion:Compound 4h was the most active compound and could act as a prospective lead molecule for anticancer agent.

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Phytochemical and Pharmacological Review on Two Herbs of Baijiangcao: Patrinia scabiosaefolia Fisch. ex Trev. and Patrinia villosa (Thunb.) Juss

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x16666190617161124 ◽

2020 ◽

Vol 17 (5) ◽

pp. 496-517

Author(s):

Yangcheng Liu ◽

Wei Liu ◽

Jiaqi Wang ◽

Yang Liu ◽

Changlan Chen ◽

...

Keyword(s):

Chemical Constituents ◽

Volatile Components ◽

Research Papers ◽

Pharmacological Activities ◽

Comprehensive Review ◽

Scientific Databases ◽

The Past ◽

Current State ◽

Patrinia Scabiosaefolia ◽

Antiviral Activities

Patrinia scabiosaefolia Fisch. Trev. and Patrinia villosa (Thunb.) Juss, are two species of Patrinia recorded in the Chinese Pharmacopoeia with the same Chinese name “Baijiangcao” and similar therapeutic effect in traditional Chinese medicine. The present article is the first comprehensive review on the chemical composition and pharmacological activities of these herbs. In this review, data on chemical constituents and pharmacological profile of the two herbs are provided. This review discusses all the classes of the 223 compounds (phenylpropanoids, flavonoids, terpenes, saponins and volatile components, etc.) detected in the two herbs providing information on the current state of knowledge of the phytochemicals present in them. In the past three years, our research group has isolated and identified about more than 100 ingredients from the two herbs. Therefore, we published a systematic review of our research papers and studies on the two herbs were carried out using resources such as classic books about Chinese herbal medicine and scientific databases including Pubmed, Web of Science, SciFinder, CNKI. etc. The present review discusses the most thoroughly studied pharmacological activities (antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, antitumor and antiviral activities) of the two herbs. This comprehensive review will be informative for scientists searching for new properties of these herbs and will be important and significant for the discovery of bioactive compounds from the two herbs and in complete utilization of Patrinia scabiosaefolia Fisch. ex Trev. and Patrinia villosa (Thunb.) Juss.

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