Marine Sulfated Polysaccharides as Promising Antiviral Agents: A Comprehensive Report and Modeling Study Focusing on SARS CoV-2

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2′s spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein’s RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.

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Antiviral Strategies Using Natural Source-Derived Sulfated Polysaccharides in the Light of the COVID-19 Pandemic and Major Human Pathogenic Viruses

Viruses ◽

10.3390/v14010035 ◽

2021 ◽

Vol 14 (1) ◽

pp. 35

Author(s):

Bimalendu Ray ◽

Imran Ali ◽

Subrata Jana ◽

Shuvam Mukherjee ◽

Saikat Pal ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Infection ◽

Molecular Mechanisms ◽

Viral Infections ◽

Structural Characteristics ◽

Antiviral Agents ◽

Host Cells ◽

Sulfated Polysaccharides ◽

Susceptible Host ◽

Pathogenic Viruses

Only a mere fraction of the huge variety of human pathogenic viruses can be targeted by the currently available spectrum of antiviral drugs. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the urgent need for molecules that can be deployed quickly to treat novel, developing or re-emerging viral infections. Sulfated polysaccharides are found on the surfaces of both the susceptible host cells and the majority of human viruses, and thus can play an important role during viral infection. Such polysaccharides widely occurring in natural sources, specifically those converted into sulfated varieties, have already proved to possess a high level and sometimes also broad-spectrum antiviral activity. This antiviral potency can be determined through multifold molecular pathways, which in many cases have low profiles of cytotoxicity. Consequently, several new polysaccharide-derived drugs are currently being investigated in clinical settings. We reviewed the present status of research on sulfated polysaccharide-based antiviral agents, their structural characteristics, structure–activity relationships, and the potential of clinical application. Furthermore, the molecular mechanisms of sulfated polysaccharides involved in viral infection or in antiviral activity, respectively, are discussed, together with a focus on the emerging methodology contributing to polysaccharide-based drug development.

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The roles of vitamin D in increasing the body's immunity and reducing injuries due to viral infections: With an emphasis on its possible role in SARS-CoV-2 (COVID-19)

Current Pharmaceutical Design ◽

10.2174/1381612827666210608145236 ◽

2021 ◽

Vol 27 ◽

Author(s):

Elahe Aleebrahim-Dehkordi ◽

Niloofar Deravi ◽

Shirin Yaghoobpoor ◽

Dariush Hooshyar ◽

Mahmoud Rafieian-Kopaei

Keyword(s):

Vitamin D ◽

Immune System ◽

Vitamin D Deficiency ◽

Viral Infections ◽

Vitamin D Supplementation ◽

Angiotensin Converting Enzyme 2 ◽

Treatment And Prevention ◽

Lung Injuries ◽

Novel Coronavirus ◽

Cytochrome P450 Family

Background: It is known that Vitamin D can increase the body’s immunity against some viral infections. Many people around the world have vitamin D deficiency and, therefore, this has become a public concern whether vitamin D is an important factor protecting against COVID-19 infection. In this paper, the data about the roles of vitamin D on immunity and recovery from viral infections, especially novel Coronavirus disease (COVID-19) is reviewed. Methods: The electronic databases of Pubmed, Google Scholar, Research Gate, Excerpta Media Database (EMBASE) and Medical and Health Education (Medrix) were searched. Results: Vitamin D is considered an important factor in immune homeostasis. Various effects have been considered for this nutrient on the immune system, particularly because of vitamin D receptor (VDR) and Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) expression in most of the immune cells. Vitamin D can raise cellular immunity, reduce cytokine storm and enhance antioxidants production. It also has modulatory effects on Angiotensin-converting enzyme 2 (ACE2) receptors and might have protective functions against acute lung injuries, including COVID-19 infection. However, there are some articles against this positive effect. Conclusion: Vitamin D supplementation is reported to be effective in the enhancement of the immune system and might be effective in the treatment and prevention of COVID-19 infection, especially in those with its deficiency. However, it should be considered that vitamin D deficiency shows the overall health status of the patients and cannot be considered specific for COVID-19 infection.

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A silkworm–baculovirus model for assessing the therapeutic effects of antiviral compounds: characterization and application to the isolation of antivirals from traditional medicines

Journal of General Virology ◽

10.1099/vir.0.83208-0 ◽

2008 ◽

Vol 89 (1) ◽

pp. 188-194 ◽

Cited By ~ 29

Author(s):

Yutaka Orihara ◽

Hiroshi Hamamoto ◽

Hiroshi Kasuga ◽

Toru Shimada ◽

Yasushi Kawaguchi ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Infections ◽

Antiviral Agents ◽

Vero Cells ◽

Infection Model ◽

Nuclear Magnetic Resonance Analysis ◽

Therapeutic Effects ◽

Traditional Medicines ◽

Baculovirus Infection ◽

Simplex Virus

Ganciclovir, foscarnet, vidarabine and ribavirin, which are used to treat viral infections in humans, inhibited the proliferation of a baculovirus (Bombyx mori nucleopolyhedrovirus) in BmN4 cells, a cultured silkworm cell line. These antiviral agents inhibited the proliferation of baculovirus in silkworm body fluid and had therapeutic effects. Using the silkworm infection model, the antiviral activity of Kampo medicines was screened and it was found that cinnamon bark, a component of the traditional Japanese medicine Mao-to, had a therapeutic effect. Based on the therapeutic activity, the antiviral substance was purified. Nuclear magnetic resonance analysis of the purified fraction revealed that the antiviral activity was due to cinnzeylanine, which has previously been isolated from Cinnamomum zeylanicum. Cinnzeylanine inhibits the proliferation of herpes simplex virus type 1 in Vero cells. These results suggest that the silkworm–baculovirus infection model is useful for screening antiviral agents that are effective for treating humans infected with DNA viruses.

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Seaweed Sulfated Polysaccharides against Respiratory Viral Infections

Pharmaceutics ◽

10.3390/pharmaceutics13050733 ◽

2021 ◽

Vol 13 (5) ◽

pp. 733

Author(s):

Mehwish Jabeen ◽

Mélody Dutot ◽

Roxane Fagon ◽

Bernard Verrier ◽

Claire Monge

Keyword(s):

Side Effects ◽

Antiviral Activity ◽

Viral Infections ◽

Specific Treatment ◽

Respiratory Viruses ◽

Sulfated Polysaccharides ◽

Safe Alternative ◽

Synthetic Drugs ◽

Different Types ◽

Respiratory Viral Infections

Respiratory viral infections have been a leading cause of morbidity and mortality worldwide. Despite massive advancements in the virology field, no specific treatment exists for most respiratory viral infections. Approved therapies against respiratory viruses rely almost exclusively on synthetic drugs that have potential side effects, restricting their use. This review aims to present natural marine sulfated polysaccharides possessing promising antiviral activity against respiratory viruses that could be a safe alternative to synthetic broad-spectrum antiviral drugs. The antiviral properties of marine sulfated polysaccharides are presented according to their mechanism of action on different types and strains of respiratory viruses, and the potential limits of their use are discussed.

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Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

Molecules ◽

10.3390/molecules26082235 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2235

Author(s):

Anastasiya S. Sokolova ◽

Valentina P. Putilova ◽

Olga I. Yarovaya ◽

Anastasiya V. Zybkina ◽

Ekaterina D. Mordvinova ◽

...

Keyword(s):

Influenza Virus ◽

Antiviral Activity ◽

Rational Design ◽

Ebola Virus ◽

Viral Infections ◽

Antiviral Agents ◽

Antiviral Drug ◽

Surface Proteins ◽

Hantaan Virus

To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC50 = 45.3 µM), Ebola pseudotype viruses (IC50 = 0.12 µM), and authentic EBOV (IC50 = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC50 = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.

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Research Progress on the Cardiac Injury from ACE2 Targeting in SARS-CoV-2 Infection

Biomolecules ◽

10.3390/biom11020196 ◽

2021 ◽

Vol 11 (2) ◽

pp. 196

Author(s):

Hao Sun ◽

Xiaojuan Su ◽

Lingyi Huang ◽

Dezhi Mu ◽

Yi Qu

Keyword(s):

Structural Characteristics ◽

Antiviral Agents ◽

Cardiac Injury ◽

Research Progress ◽

The Novel ◽

Angiotensin Converting Enzyme 2 ◽

Target Organs ◽

Therapeutic Measures ◽

Novel Coronavirus ◽

Cardiac Manifestations

The epidemic due to the novel coronavirus (SARS-CoV-2) is now a global concern, posing a severe threat to the health of populations. At present, all countries in the world are stepping up the development of vaccines and antiviral agents to prevent the infection and further transmission of SARS-CoV-2. An in-depth investigation of the target organs and pathogenesis regarding SARS-CoV-2 infection will be beneficial for virus therapy. Besides pulmonary injury, SARS-CoV-2 also causes cardiac injury, but the exact mechanisms are unclear. This review summarizes the essential structural characteristics of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2), describes the cardiac manifestations following SARS-CoV-2 infection, and explores the mechanisms of cardiac injury targeting ACE2 after the viral invasion. We aim to help the timely detection of related symptoms and implementation of therapeutic measures by clinicians for SARS-CoV-2 infection.

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Inhibition of SARS-CoV-2 Virus Entry by the Crude Polysaccharides of Seaweeds and Abalone Viscera In Vitro

Marine Drugs ◽

10.3390/md19040219 ◽

2021 ◽

Vol 19 (4) ◽

pp. 219

Author(s):

Sung-Kun Yim ◽

Kian Kim ◽

Inhee Kim ◽

SangHo Chun ◽

TaeHwan Oh ◽

...

Keyword(s):

Antiviral Activity ◽

Virus Entry ◽

Antiviral Agents ◽

Laminaria Japonica ◽

Sulfated Polysaccharides ◽

Total Carbohydrate ◽

Porphyra Tenera ◽

Antiviral Activities ◽

Crude Polysaccharide

Much attention is being devoted to the potential of marine sulfated polysaccharides as antiviral agents in preventing COVID-19. In this study, sulfated fucoidan and crude polysaccharides, extracted from six seaweed species (Undaria pinnatifida sporophyll, Laminaria japonica, Hizikia fusiforme, Sargassum horneri, Codium fragile, Porphyra tenera) and Haliotis discus hannai (abalone viscera), were screened for their inhibitory activity against SARS-CoV-2 virus entry. Most of them showed significant antiviral activities at an IC50 of 12~289 μg/mL against SARS-CoV-2 pseudovirus in HEK293/ACE2, except for P. tenera (IC50 > 1000 μg/mL). The crude polysaccharide of S. horneri showed the strongest antiviral activity, with an IC50 of 12 μg/mL, to prevent COVID-19 entry, and abalone viscera and H. fusiforme could also inhibit SARS-CoV-2 infection with an IC50 of 33 μg/mL and 47 μg/mL, respectively. The common properties of these crude polysaccharides, which have strong antiviral activity, are high molecular weight (>800 kDa), high total carbohydrate (62.7~99.1%), high fucose content (37.3~66.2%), and highly branched polysaccharides. These results indicated that the crude polysaccharides from seaweeds and abalone viscera can effectively inhibit SARS-CoV-2 entry.

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Targeting novel coronavirus SARS-CoV-2 spike protein with phytoconstituents of Momordica charantia

Journal of Ovarian Research ◽

10.1186/s13048-021-00872-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Santosh Kumar Singh ◽

Shailesh Singh ◽

Rajesh Singh

Keyword(s):

Viral Infections ◽

Hydrophobic Interactions ◽

Docking Study ◽

Docking Studies ◽

Momordica Charantia ◽

Spike Protein ◽

Strong Interactions ◽

Bitter Melon ◽

Novel Coronavirus ◽

Potential Interactions

Abstract Background Infections by the SARS-CoV-2 virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives. Hence, in this study, we identified phytoconstituents of an edible vegetable, Bitter melon (Momordica charantia), that affect the SARS-CoV-2 spike protein. Methods Components of Momordica charantia were tested to identify the compounds that bind to the SARS-CoV-2 spike protein. An MTiOpenScreen web-server was used to perform docking studies. The Lipinski rule was utilized to evaluate potential interactions between the drug and other target molecules. PyMol and Schrodinger software were used to identify the hydrophilic and hydrophobic interactions. Surface plasmon resonance (SPR) was employed to assess the interaction between an extract component (erythrodiol) and the spike protein. Results Our in-silico evaluations showed that phytoconstituents of Momordica charantia have a low binding energy range, -5.82 to -5.97 kcal/mol. A docking study revealed two sets of phytoconstituents that bind at the S1 and S2 domains of SARS-CoV-2. SPR showed that erythrodiol has a strong binding affinity (KD = 1.15 μM) with the S2 spike protein of SARS-CoV-2. Overall, docking, ADME properties, and SPR displayed strong interactions between phytoconstituents and the active site of the SARS-CoV-2 spike protein. Conclusion This study reveals that phytoconstituents from bitter melon are potential agents to treat SARS-CoV-2 viral infections due to their binding to spike proteins S1 and S2.

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Antiviral and Immunological Activity of Zinc and Possible Role in COVID-19

British Journal Of Nutrition ◽

10.1017/s0007114521002099 ◽

2021 ◽

pp. 1-21

Author(s):

D.N. Marreiro ◽

K.J.C. Cruz ◽

A.R.S. Oliveira ◽

J.B.S. Morais ◽

B.J.S.A. Freitas ◽

...

Keyword(s):

Immune System ◽

Antiviral Activity ◽

Viral Infections ◽

Antiviral Agents ◽

Experimental Studies ◽

Case Series ◽

The Body ◽

Case Control Studies ◽

Letters To The Editor ◽

Tract Infections

Abstract Zinc deficiency compromises its biological functions, its effect on the immune system and its antiviral activity, increasing vulnerability to infectious diseases. This narrative review aims at presenting and discussing functional aspects and possible mechanisms involved in the potential role of zinc in the immune response and antiviral activity for COVID-19 prevention and control. The searches were conducted in PubMed and Science Direct databases, using clinical trials, experimental studies in animals and humans, case-control studies, case series, letters to the editor, and review articles published in English, without restrictions on year of publication. Search approach was based on using the terms: “zinc”, “COVID-19”, “antiviral agents”, “immunologic factors”, and “respiratory tract infections”. Literature shows the importance of zinc as an essential mineral immunomodulator with relevant antiviral activity in the body. Thus, although there is still a scarcity of studies evaluating zinc supplementation in patients with COVID-19, the results on the topic show the necessity of controlling zinc mineral deficiency, as well as maintaining its homeostasis in the body in order to strengthen the immune system and improve the prevention of highly-complex viral infections, such as that of the COVID-19.

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African and Asian Medicinal Plants as a Repository for Prospective Antiviral Metabolites Against HIV-1 and SARS CoV-2: A Mini Review

Frontiers in Pharmacology ◽

10.3389/fphar.2021.703837 ◽

2021 ◽

Vol 12 ◽

Author(s):

Godwin Anywar ◽

Muhammad Akram ◽

Muhammad Amjad Chishti

Keyword(s):

Medicinal Plants ◽

Plant Species ◽

Viral Infections ◽

Antiviral Agents ◽

Natural Compounds ◽

Drug Candidates ◽

Novel Coronavirus ◽

Hiv 1

Introduction: The worldwide burden of viral infections has triggered a resurgence in the search for new and more efficient antiviral drugs. Scientists are also repurposing existing natural compounds such as the antimalarial drug artemisinin from Artemesia annua L. as potential drug candidates for some of the emerging and re-emerging viral infections such as covid-19Aim: The aim of this review was to analyse the existing literature to explore the actual or potential natural antiviral compounds from African and Asian medicinal plants as lead compounds in the drug discovery process.Methods: We searched the literature on African and Asian medicinal plant species as antiviral agents for HIV-1 and the novel coronavirus (SARS-CoV-2) in various databases and search engines such as Web of Science, Google Scholar and PubMed. The search was limited to in vitro, in vivo, and clinical studies and excluded in silico studies.Results: We present 16 plant species with actual or potential antiviral activity against HIV-1 and SARS-CoV-2. These plant species span the continents of Africa and Asia where they are widely used for treating several other ailments.Conclusion: Natural compounds from plants can play a significant role in the clinical management of HIV/AIDS and the covid-19 pandemic. More research needs to be conducted to investigate the potential toxicities of the various compounds and their efficacies in clinical settings.

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