Anisotine and amarogentin as promising inhibitory candidates against SARS-CoV-2 proteins: a computational investigation

Kar, Pallab; Kumar, Vijay; Vellingiri, Balachandar; Sen, Arnab; Jaishee, Nishika; Anandraj, Akash; Malhotra, Himani; Bhattacharyya, Subires; Mukhopadhyay, Subhasish; Kinoshita, Masako; Govindasamy, Vivekanandhan; Roy, Ayan; Naidoo, Devashan; Subramaniam, Mohana Devi

doi:10.1080/07391102.2020.1860133

Cited by 46 publications

(30 citation statements)

References 47 publications

(104 reference statements)

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“…On the contrary, the free spike, M pro and PL pro proteins were noted to display considerable fluctuations throughout the timescale of the MD simulations and returned average RMSD values of 1.9 Å, 1.5 Å and 1.8 Å, respectively (Figures 5A, 6A and 7A). It has been suggested that lower RMSD values reflect higher conformational stability of protein-protein complexes [22,27]. The present findings reflected the decent binding potential of cyanovirin-N with the SARS-CoV-2 proteins and emphasized the fact that the binding of cyanovirin-N to the viral proteins imparted considerable stability to the complexes [21].…”

Section: Analysis Of Molecular Dynamics Simulations Of the Protein-protein Complexessupporting

confidence: 63%

“…The binding efficacies of the cyanobacterial proteins with SARS-CoV-2 M pro were further compared with the interaction profile of the Michael acceptor (peptidyl) inhibitor that has been recently reported to exhibit significant inhibitory efficacy against the SARS-CoV-2 M pro [37]. Quite interestingly, the cyanobacterial proteins displayed significantly higher (p < 0.01) binding energy scores than the Michael acceptor (peptidyl) inhibitor-SARS-CoV-2 M pro complex (−7.1 kcal/mol) (Table 1) [27]. Furthermore, the electrophilicity of α and β unsaturated systems suggests that the Michael acceptor may interact with off-target proteins [46].…”

Section: Molecular Docking Of the Cyanobacterial Proteins With The Sars-cov-2 M Promentioning

confidence: 99%

“…Recently, several peptide inhibitors of SARS-CoV-2 proteins were proposed as therapeutic remedies against COVID-19 and are presently under preclinical evaluation [23][24][25][26]. In the present study, we investigated the potential for the inhibition of the SARS-CoV-2 spike protein, M pro and PL pro [27,28] by antiviral cyanobacterial proteins; cyanovirin-N [29], scytovirin [30] and phycocyanin [31] employing molecular docking approach. The rationale for selecting the inhibitory targets in SARS-CoV-2 has been depicted in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

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Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, Mpro and PLpro of SARS-CoV-2: Protein–Protein Interactions, Dynamics Simulations and Free Energy Calculations

et al. 2021

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The emergence of COVID-19 continues to pose severe threats to global public health. The pandemic has infected over 171 million people and claimed more than 3.5 million lives to date. We investigated the binding potential of antiviral cyanobacterial proteins including cyanovirin-N, scytovirin and phycocyanin with fundamental proteins involved in attachment and replication of SARS-CoV-2. Cyanovirin-N displayed the highest binding energy scores (−16.8 ± 0.02 kcal/mol, −12.3 ± 0.03 kcal/mol and −13.4 ± 0.02 kcal/mol, respectively) with the spike protein, the main protease (Mpro) and the papainlike protease (PLpro) of SARS-CoV-2. Cyanovirin-N was observed to interact with the crucial residues involved in the attachment of the human ACE2 receptor. Analysis of the binding affinities calculated employing the molecular mechanics-Poisson–Boltzmann surface area (MM-PBSA) approach revealed that all forms of energy, except the polar solvation energy, favourably contributed to the interactions of cyanovirin-N with the viral proteins. With particular emphasis on cyanovirin-N, the current work presents evidence for the potential inhibition of SARS-CoV-2 by cyanobacterial proteins, and offers the opportunity for in vitro and in vivo experiments to deploy the cyanobacterial proteins as valuable therapeutics against COVID-19.

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Section: Analysis Of Molecular Dynamics Simulations Of the Protein-protein Complexessupporting

confidence: 63%

Section: Molecular Docking Of the Cyanobacterial Proteins With The Sars-cov-2 M Promentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, Mpro and PLpro of SARS-CoV-2: Protein–Protein Interactions, Dynamics Simulations and Free Energy Calculations

et al. 2021

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“…Individuals with chronic diabetes accompanied with foot ulcers are prone to this infection as any injured skin tissue is an easy entry route for this fungus. Further, treatment for COVID-19 is still preliminary ( Kar et al, 2020 ; Kinoshita et al, 2021 ), and to combat the effect of SARS-CoV-2 infection, patients are given heavy doses of steroids (corticosteroids), as it reduces the inflammation in the lungs and might also curb the damages that had happened in the body due to the cytokine storm. Meanwhile patients affected with this new strain of COVID-19 are mostly treated with heavy steroids, extreme use of oxygen masks and ventilators which makes these patients more susceptible to mucormycosis.…”

Section: Possible Role Of Action Of Mucormycosis Among Covid-19 Patientsmentioning

confidence: 99%

Mucormycosis: An opportunistic pathogen during COVID-19

Iyer¹,

Jayaramayya

Venkatesan

et al. 2021

Environmental Research

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154

122

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The pandemic of coronavirus disease 2019 (COVID-19) still remains on an upsurge trend. The second wave of this disease has led to panic in many countries, including India and some parts of the world suffering from the third wave. As there are no proper treatment options or remedies available for this deadly infection, supportive care equipment's such as oxygen cylinders, ventilators and heavy use of steroids play a vital role in the management of COVID-19. In the midst of this pandemic, the COVID-19 patients are acquiring secondary infections such as mucormycosis also known as black fungus disease. Mucormycosis is a serious, but rare opportunistic fungal infection that spreads rapidly, and hence prompt diagnosis and treatment are necessary to avoid high rate of mortality and morbidity rates. Mucormycosis is caused by the inhalation of its filamentous (hyphal form) fungi especially in the patients who are immunosuppressed. Recent studies have documented alarming number of COVID-19 patients with mucormycosis infection. Most of these patients had diabetes and were administered steroids for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and were consequently more prone to mucormycosis. Hence, the present review emphasizes mucormycosis and its related conditions, its mechanism in normal and COVID-19 affected individuals, influencing factors and challenges to overcome this black mold infection. Early identification and further investigation of this fungus will significantly reduce the severity of the disease and mortality rate in COVID-19 affected patients.

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“…The binding affinity of anisotine as a quinazoline alkaloid of the leaves of Justicia adhatoda L. (Acanthaceae) to SARS-CoV-2 Mpro was reported to be −7.9 kcal/mol that was stronger than that of darunavir and lopinavir, as positive control drugs [ 59 ]. Besides, Kar et al showed the predicted the inhibitory constant (Ki) of anisotine interaction with Mpro, S proteins, and RdRp of SARS-CoV-2 was 1.90 μ M, 0.70 μ M, and 47.08 μ M, respectively [ 60 ].…”

Section: Alkaloids As Potential Phytochemicals Against Sars-cov-2mentioning

confidence: 99%

Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms

Majnooni

Fakhri

Bahrami

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Since its inception, the coronavirus disease 2019 (COVID-19) pandemic has infected millions of people around the world. Therefore, it is necessary to find effective treatments against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), as it is the viral source of COVID-19. Alkaloids are one of the most widespread plant-derived natural compounds with prominent antiviral effects. Accordingly, these phytochemicals have been promising candidates towards discovering effective treatments for COVID-19. Alkaloids have shown potential anti-SARS-CoV activities via inhibiting pathogenesis-associated targets of the Coronaviridae family that are required for the virus life cycle. In the current study, the chemistry, plant sources, and antiviral effects of alkaloids, as well as their anti-SARS-CoV-2 effect with related mechanisms, are reviewed towards discovering an effective treatment against COVID-19.

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Anisotine and amarogentin as promising inhibitory candidates against SARS-CoV-2 proteins: a computational investigation

Cited by 46 publications

References 47 publications

Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, Mpro and PLpro of SARS-CoV-2: Protein–Protein Interactions, Dynamics Simulations and Free Energy Calculations

Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, Mpro and PLpro of SARS-CoV-2: Protein–Protein Interactions, Dynamics Simulations and Free Energy Calculations

Mucormycosis: An opportunistic pathogen during COVID-19

Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms

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