scholarly journals Anti-SARS-CoV-2 potential of Cissampelos pareira L. identified by Connectivity map-based analysis and in vitro studies

2021 ◽  
Author(s):  
Madiha Haider ◽  
Vivek Anand ◽  
Dhwani Dholakia ◽  
M Ghalib Enayathullah ◽  
Yash Parekh ◽  
...  

Background: Viral infections have a history of abrupt and severe eruptions through the years in the form of pandemics. And yet, definitive therapies or preventive measures are not present. Purpose: Herbal medicines have been a source of various antiviral compounds. An accelerated repurposing potential of antiviral herbs can provide usable drugs and identify druggable targets. In this study, we dissect the anti-coronavirus activity of Cissampelos pareira L (Cipa). using an integrative approach. Methods: We analyzed the signature similarities between predicted antiviral agents and Cipa using the connectivity map (https://clue.io/). Next, we tested the anti-SARS-COV-2 activity of Cipa in vitro. A three-way comparative analysis of Cipa transcriptome, COVID-19 BALF transcriptome and CMAP signatures of small compounds was also performed. Results: Several predicted antivirals showed a high positive connectivity score with Cipa such as apcidin, emetine, homoharringtonine etc. We also observed 98% inhibition of SARS-COV-2 replication in infected Vero cell cultures with the whole extract. Some of its prominent pure constituents e.g pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. Comparison of genes between BALF and Cipa showed an enrichment of biological processes like transcription regulation and response to lipids, to be downregulated in Cipa while being upregulated in COVID-19. CMAP also showed that Triciribine, torin-1 and VU-0365114-2 had positive connectivity with BALF 1 and 2, and negative connectivity with Cipa.

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3868
Author(s):  
Rambod Abiri ◽  
Hazandy Abdul-Hamid ◽  
Oksana Sytar ◽  
Ramin Abiri ◽  
Eduardo Bezerra de Almeida ◽  
...  

The COVID-19 pandemic, as well as the more general global increase in viral diseases, has led researchers to look to the plant kingdom as a potential source for antiviral compounds. Since ancient times, herbal medicines have been extensively applied in the treatment and prevention of various infectious diseases in different traditional systems. The purpose of this review is to highlight the potential antiviral activity of plant compounds as effective and reliable agents against viral infections, especially by viruses from the coronavirus group. Various antiviral mechanisms shown by crude plant extracts and plant-derived bioactive compounds are discussed. The understanding of the action mechanisms of complex plant extract and isolated plant-derived compounds will help pave the way towards the combat of this life-threatening disease. Further, molecular docking studies, in silico analyses of extracted compounds, and future prospects are included. The in vitro production of antiviral chemical compounds from plants using molecular pharming is also considered. Notably, hairy root cultures represent a promising and sustainable way to obtain a range of biologically active compounds that may be applied in the development of novel antiviral agents.


Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 600 ◽  
Author(s):  
Constanza Cárdenas ◽  
Fanny Guzmán ◽  
Marisela Carmona ◽  
Cristian Muñoz ◽  
Luis Nilo ◽  
...  

Viral infections in salmonids represent an ongoing challenge for the aquaculture industry. Two RNA viruses, the infectious pancreatic necrosis virus (IPNV) and the infectious salmon anemia virus (ISAV), have become a latent risk without healing therapies available for either. In this context, antiviral peptides emerge as effective and relatively safe therapeutic molecules. Based on in silico analysis of VP2 protein from IPNV and the RNA-dependent RNA polymerase from ISAV, a set of peptides was designed and were chemically synthesized to block selected key events in their corresponding infectivity processes. The peptides were tested in fish cell lines in vitro, and four were selected for decreasing the viral load: peptide GIM182 for IPNV, and peptides GIM535, GIM538 and GIM539 for ISAV. In vivo tests with the IPNV GIM 182 peptide were carried out using Salmo salar fish, showing a significant decrease of viral load, and proving the safety of the peptide for fish. The results indicate that the use of peptides as antiviral agents in disease control might be a viable alternative to explore in aquaculture.


2008 ◽  
Vol 1 ◽  
pp. VRT.S527
Author(s):  
William A. Cafruny ◽  
Richard G. Duman ◽  
Raymond R. Rowland ◽  
Eric A. Nelson ◽  
Grace H. Wong

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically significant agent for which there currently are no effective treatments. Development of antiviral agents for PRRSV as well as many other viruses has been limited by toxicity of known antiviral compounds. In contrast, antibiotics for non-virus microbial infections have been widely useful, in part because of their acceptable toxicity in animals. We report here the discovery that the quinolone-containing compound Plasmocin™, as well as the quinolones nalidixic acid and ciprofloxacin, have potent anti-PRRSV activity in vitro. PRRSV replication was inhibited by these antibiotics in both cultured MARC-145 cells and cultured primary alveolar porcine macrophages (PAMs). Furthermore, sub-optimal concentrations of nalidixic acid synergized with antiviral cytokines (AK-2 or IFN-γ) to quantitatively and qualitatively inhibit PRRSV replication in MARC-145 cells or PAMs. The antiviral activity of Plasmocin and nalidixic acid correlated with reduced actin expression in MARC-145 cells. Replication of the related lactate dehydrogenase-elevating virus (LDV) was also inhibited in primary mouse macrophages by Plasmocin. These results are significant to the development of antiviral strategies with potentially reduced toxicity, and provide a model system to better understand regulation of arterivirus replication.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
I. Relaño-Rodríguez ◽  
M. S. Espinar-Buitrago ◽  
V. Martín-Cañadilla ◽  
R. Gómez-Ramirez ◽  
J. L. Jiménez ◽  
...  

Abstract Background Human cytomegalovirus (HCMV) is a worldwide infection, causing different troublesome in immunosupressed patients and very related to Human Immunodeficiency Virus 1 (HIV-1) infection, mainly in developing countries, with a co-infection rate of 80% in Africa. The high cost of present treatments and the lack of routinely tests in these countries urge the necessity to develop new molecules or strategies against HCMV. The new treatments should be low-cost and capable of avoiding the emerging problem of resistant virus. Nanoparticles play an important role in several viral infections. Our main focus is to study the potential activity of polyanionic carbosilane dendrimers (PDC), which are hyperbranched molecules with several sulfonate or sulfate groups in their periphery, against different viruses. Results We studied the activity of G1-S4, G2-S16 and G2-S24P PDCs in MRC-5 cell line against HCMV infection by several plaque reduction assays. Our results show that dendrimers present good biocompatibility at the concentrations tested (1–50 µM) for 6 days in cell culture. Interestingly, both G2-S16 and G2-S24P showed a remarked inhibition at 10 µM against HCMV infection. Results on attachment and virucidal assays indicated that the inhibition was not directed to the virus or the virus-cell attachment. However, results of time of addition, showed a longer lasting activity of these dendrimers in comparison to ganciclovir, and the combination of G2-S16 or G2-S24P with ganciclovir increases the HCMV inhibition around 90 %. Conclusions Nanotechnology, in particular polyanionic carbosilane dendrimers, have proved their potential application against HCMV, being capable of inhibiting the infection by themselves or enhancing the activity of ganciclovir, the actual treatment. These compounds represent a low-cost approach to fight HCMV infections.


2021 ◽  
Vol 9 (Spl-1- GCSGD_2020) ◽  
pp. S43-S48
Author(s):  
Manishaa Sri Mahendran ◽  
◽  
Sinouvassane Djearamane ◽  
Ling Shing Wong ◽  
Govindaraju Kasivelu ◽  
...  

The recent outbreak of Corona Virus Disease (COVID-19) and the surge in accelerating the development of a vaccine to fight against the SARS-CoV-2 virus has imposed greater challenges to humanity worldwide. There is lack of research into the production of effective vaccines and methods of treatment against viral infections. As of now, strategies encompassing antiviral drugs and corticosteroids alongside mechanical respiratory treatment are in practice as frontline treatments. Though studies have reported that microalgae possess antiviral properties, only a few cases have presented the existence of antiviral compounds such as algal polysaccharides, lectins, aggluttinins, scytovirin, algal lipids such as sulfoquinovosyldiacylglycerol (SQDG), monogalactosyldiacylglycerides (MGDG) and digalactosyldiacylglycerides (DGDG), and algal biopigments especially chlorophyll analogues, marennine, phycobiliproteins, phycocyanin, phycoerythrin and allophycocyanin that are derived from marine and freshwater microalgae. Given the chemodiversity of bioactive compounds from microalgae and the present scenario, algal biotechnology is seen as a prospective source of antiviral and anti-inflammatory compounds that can be used to develop antiviral agents. Microalgae with potential as antivirals and microalgae derived functional compounds to treat viral diseases are summarized and can be used as a reference in developing algae-derived antivirals to treat SARS-CoV-2 and other similar viruses.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ken Watanabe

Influenza virus infections are a serious public health concern throughout the world. Emergence of viral resistance to the currently approved anti-influenza drugs warrants the development of new antiviral agents. Japanese herbal medicines called Kampo are very commonly used as prescription medication in Japan, and Mao-to is known to be effective against influenza that is caused by oseltamivir-resistant viruses. However, influenza-related death occurs mainly among the elderly, and for patients with hypertension and diabetes, Mao-to may cause these diseases to worsen. Therefore, the exploration of more potent and safe Kampo medicines may be a good strategy for developing new influenza medicines. Here cell-based screening of anti-influenza virus activity for 42 approved Kampo medicines was performed using the drug-repositioning approach. As a result, four Kampo medicines were selected as potent anti-influenza agents against the A/WSN/33 strain. It was found that Daio-kanzo-to [50% inhibitory concentration (IC50) = 10.5 μg/mL; 50% cytotoxic concentration (CC50) = 71.6 μg/mL; selective index = 6.8] is more effective than Mao-to. Daio-kanzo-to and its constituent Japanese Pharmacopoeia (JP) Rhubarb were also effective against H3N2 and H1N1 subtypes of influenza viruses, including oseltamivir-insensitive-2009 pandemic clinical isolates. These data suggest the potential application of Daio-kanzo-to for influenza treatment.


Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2235
Author(s):  
Anastasiya S. Sokolova ◽  
Valentina P. Putilova ◽  
Olga I. Yarovaya ◽  
Anastasiya V. Zybkina ◽  
Ekaterina D. Mordvinova ◽  
...  

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.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 171 ◽  
Author(s):  
Florina-Daniela Cojocaru ◽  
Doru Botezat ◽  
Ioannis Gardikiotis ◽  
Cristina-Mariana Uritu ◽  
Gianina Dodi ◽  
...  

Viral infections are a major global health problem, representing a significant cause of mortality with an unfavorable continuously amplified socio-economic impact. The increased drug resistance and constant viral replication have been the trigger for important studies regarding the use of nanotechnology in antiviral therapies. Nanomaterials offer unique physico-chemical properties that have linked benefits for drug delivery as ideal tools for viral treatment. Currently, different types of nanomaterials namely nanoparticles, liposomes, nanospheres, nanogels, nanosuspensions and nanoemulsions were studied either in vitro or in vivo for drug delivery of antiviral agents with prospects to be translated in clinical practice. This review highlights the drug delivery nanosystems incorporating the major antiviral classes and their transport across specific barriers at cellular and intracellular level. Important reflections on nanomedicines currently approved or undergoing investigations for the treatment of viral infections are also discussed. Finally, the authors present an overview on the requirements for the design of antiviral nanotherapeutics.


2022 ◽  
Vol 6 (1) ◽  
pp. 01-07
Author(s):  
Abbaraju Krishna Sailaja ◽  
Amand Alekhya

The term “Antiviral agents” has been defined in very wide terms as substances other than a virus or virus containing vaccine or specific antibody which can build either a protective or therapeutic effect to the direct measurable advantage of the virus infected host. Viruses are simple in form which are very tiny germs. They comprise of genetic material inside of a protein coating. Viruses cause amicable infectious diseases like common cold, flu and warts. They also cause severe diseases such as HIV/AIDS, Ebola, avian influenzas, dengue virus and COVID-19. Viral diseases are very complex and are easily spread. Herbs and herbal medicines were the foremost in treating infections from centuries over the world in every civilization. Modern science has narrowed the importance of herbal medicine in the past two centuries. But, the side effects and new varieties of diseases creating challenges to modern science. So, usage of herbal medicines is again attaining interests these days. Herbal products for different treatments have achieved a lot of popularity in the last couple of decades. Thus, discovering novel antiviral drugs is of extremely important and natural products are an excellent source for such discoveries. There are many herbs which are excellent sources for the antiviral properties to treat viral infections. This review provides the verified data on the herbal substances with antiviral activity, and some of the herbal marketed antiviral agents like CORONIL TABLETS from Patanjali and different companies had made an attempt to treat viral infections in this pandemic situation. Therefore, herbal plants proved to be a major resort for the treatment of diseases and sickness by traditional healers in many societies.


2018 ◽  
Vol 6 (3) ◽  
pp. 73 ◽  
Author(s):  
Lucky Mulwa ◽  
Marc Stadler

Viral infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) pose an ongoing threat to human health due to the lack of effective therapeutic agents. The re-emergence of old viral diseases such as the recent Ebola outbreaks in West Africa represents a global public health issue. Drug resistance and toxicity to target cells are the major challenges for the current antiviral agents. Therefore, there is a need for identifying agents with novel modes of action and improved efficacy. Viral-based illnesses are further aggravated by co-infections, such as an HIV patient co-infected with HBV or HCV. The drugs used to treat or manage HIV tend to increase the pathogenesis of HBV and HCV. Hence, novel antiviral drug candidates should ideally have broad-spectrum activity and no negative drug-drug interactions. Myxobacteria are in the focus of this review since they produce numerous structurally and functionally unique bioactive compounds, which have only recently been screened for antiviral effects. This research has already led to some interesting findings, including the discovery of several candidate compounds with broad-spectrum antiviral activity. The present review looks at myxobacteria-derived antiviral secondary metabolites.


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