Promising compounds from natural sources against COVID-19

2020 ◽  
Vol 17 (2) ◽  
pp. 18-32
Author(s):  
Sergey M. Andreev ◽  
Nadezhda N. Shershakova ◽  
Ksenia V. Kozhikhova ◽  
Artyom A. Shatilov ◽  
Anastasiia V. Timofeeva ◽  
...  

The epidemic associated with the new Sars-CoV-2 coronavirus has affected almost all countries of the world and no reliable treatment for this infection exists yet. Many laboratories in the world are currently conducting intensive experimental and theoretical/in silico studies to find effective drugs specific for this disease (COVID-19), but unfortunately, it may take a long time before new drugs appear in the clinical practice. One of the currently widely accepted approaches for finding active compounds is based on the possibility of using existing drugs approved by government medical organizations (as the FDA). Their choice is based on screening, based on the use of computer models that evaluate the specific binding (energy minimization) of such drugs to target molecules that are important for the life cycle. Thus, a few well-known antiviral drugs against HIV, hepatitis C and others selected on this basis exerted an antiviral effect in vitro, but their real effectiveness was far from expected. It should be emphasized that the severe clinical manifestation of the disease is an acute respiratory distress syndrome, mediated by oxidative stress and an aggressive immune attack on its own cells. In this regard, the use of compounds with high antioxidant activity could have advantages both prophylactically and medically. There is a huge range of natural compounds, including official and traditional medicine, which represent valuable unlimited potential for COVID-19 therapy, the advantage of such compounds in their low toxicity. In this review, we tried to focus on the clinical and pharmacological properties of natural substances, mainly flavonoids, which can become promising drugs for the treatment and prevention of COVID-19. The review includes information on possible virus targets and antiviral drugs. Much attention is paid to the question of inhibition of viral activity. Based on published data, including structural features of various compounds, a prediction is made about the prospects of using these compounds as inhibitors of viral activity, as well as anti-inflammatory drugs for the treatment of COVID-19. An important step in the analysis of compounds was the study of the possibility of their interaction with cellular targets of the virus, as well as the ability to bind to the proteins of the Sars-CoV-2 virus itself.

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 144 ◽  
Author(s):  
Xiaofeng Zhai ◽  
Shilei Wang ◽  
Mengyan Zhu ◽  
Wei He ◽  
Zhongzhou Pan ◽  
...  

Porcine deltacoronavirus (PDCoV) is an emerging global swine virus that has a propensity for interspecies transmission. It was identified in Hong Kong in 2012. Given that neither specific antiviral drugs nor vaccines are available for newly emerging porcine deltacoronavirus, searching for effective antiviral drugs is a high priority. In this study, lithium chloride (LiCl) and diammonium glycyrrhizinate (DG), which are host-acting antivirals (HAAs), were tested against PDCoV. We found that LiCl and DG inhibited PDCoV replication in LLC-PK1 cells in a dose-dependent manner. The antiviral effects of LiCl and DG occurred at the early stage of PDCoV replication, and DG also inhibited virus attachment to the cells. Moreover, both drugs inhibited PDCoV-induced apoptosis in LLC-PK1 cells. This study suggests LiCl and DG as new drugs for the treatment of PDCoV infection.


2021 ◽  
Author(s):  
Dory Kovacs ◽  
Chris Davis ◽  
Paul Cannon ◽  
Melanie McFarlane ◽  
Stephanie M Rainey ◽  
...  

AbstractBackgroundSARS-CoV-2 infection, the causative agent of COVID-19, has resulted in over 2,500,000 deaths to date1. Although vaccines are becoming available, treatment options remain limited. Repurposing of compounds could reduce the time, cost, and risks associated with the development of new drugs and has been the focus of many clinical studies.Here, we summarise available evidence on 29 FDA-approved compounds, from in vitro results to clinical trials, focussing on remdesivir, galidesivir and favipiravir, and test 29 antiviral compounds’ activity in vitro.MethodsA comprehensive search strategy was used to retrieve trials and publications related to antiviral compounds with potential efficacy to treat coronaviruses. These data were used to prioritise testing of a panel of antiviral drugs in vitro against patient isolates of SARS-CoV-2. An in vitro screen was carried out to determine the activity of 29 FDA-approved compounds.Results625 clinical trials investigated 16 repurposed antiviral candidate compounds for the treatment of COVID-19. In vitro studies identified ten drug candidates with demonstrable anti-SARS-CoV-2 activity, including favipiravir, remdesivir, and galidesivir. To validate these findings, a drug screen was conducted using two cell lines and wildtype isolates of SARS-CoV-2 isolated from patients in the UK. While eight drugs with anti-SARS-CoV-2 activity were identified in vitro, activity in clinical trials has, as yet failed to demonstrate a strong effect on mortality.ConclusionsSo far, no repurposed antiviral has shown a strong effect on mortality in clinical studies. The urgent need for novel antivirals in this pandemic is clear, despite the costs and time associated with their development.Research in ContextEvidence before this studyRepurposing of existing compounds for the treatment of COVID-19 has been the focus of many in vitro studies and clinical trials, saving time, costs and risks associated with the research and development of new compounds.Added value of this studyWe reviewed the literature for 29 FDA-approved compounds with previously reported (or suspected) anti-SARS-CoV-2 activity and found 625 clinical trials that have been undertaken on 16 different drugs. We determined if repurposed antivirals are suitable for clinical trials based on previously published data, and conducted an additional in vitro screen using locally circulating strains in the UK (PHE2 and GLA1). We report the difference in IC50 from published data using Wuhan1/Wash1 strains with PHE2 and GLA1, including IC50 values below 100μM for galidesivir in wild-type virus. Given the limited success of repurposed compounds in the treatment of COVID-19, we comment on the urgent need for new antivirals specifically targeting SARS-CoV-2.Implications of all the available evidenceOur data show that most prospective compounds for repurposing show no anti-SARS-CoV-2 activity, and antiviral activity in vitro does not always translate to clinical benefit. So far, no repurposed compound has shown a strong effect on mortality in clinical studies. Drugs, including monoclonal antibody therapies, that have been developed to target SARS-CoV-2 virus itself have shown most promise.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4116
Author(s):  
Sheila C. Araujo ◽  
Fernanda S. Sousa ◽  
Thais A. Costa-Silva ◽  
Andre G. Tempone ◽  
João Henrique G. Lago ◽  
...  

In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC50 value of 4.3 μM and no observed mammalian cytotoxicity in fibroblasts (CC50 > 200 μM). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD.


2018 ◽  
Vol 24 (17) ◽  
pp. 1899-1904
Author(s):  
Daniel Fabio Kawano ◽  
Marcelo Rodrigues de Carvalho ◽  
Mauricio Ferreira Marcondes Machado ◽  
Adriana Karaoglanovic Carmona ◽  
Gilberto Ubida Leite Braga ◽  
...  

Background: Fungal secondary metabolites are important sources for the discovery of new pharmaceuticals, as exemplified by penicillin, lovastatin and cyclosporine. Searching for secondary metabolites of the fungi Metarhizium spp., we previously identified tyrosine betaine as a major constituent. Methods: Because of the structural similarity with other inhibitors of neprilysin (NEP), an enzyme explored for the treatment of heart failure, we devised the synthesis of tyrosine betaine and three analogues to be subjected to in vitro NEP inhibition assays and to molecular modeling studies. Results: In spite of the similar binding modes with other NEP inhibitors, these compounds only displayed moderate inhibitory activities (IC50 ranging from 170.0 to 52.9 µM). However, they enclose structural features required to hinder passive blood brain barrier permeation (BBB). Conclusions: Tyrosine betaine remains as a starting point for the development of NEP inhibitors because of the low probability of BBB permeation and, consequently, of NEP inhibition at the Central Nervous System, which is associated to an increment in the Aβ levels and, accordingly, with a higher risk for the onset of Alzheimer's disease.


2021 ◽  
Author(s):  
Harun ALP ◽  
Hasan ASİL ◽  
Demet Duman

Abstract Today, the coronavirus epidemic, which caused the death of 79 million cases and 1743 thousand people in 218 countries around the world, continues to increase its impact all over the world. Researchers are still trying to develop an effective solution against covid-19, including vaccines and drugs. However, there are few studies that determine the effect of natural products obtained from plants on covid-19. Medicinal and aromatic plants have been used for therapeutic purposes since the existence of humanity. In this study, the effects of some important medicinal plants including Licorice (Glycyrrhiza glabra), Saffron (Crocus sativus L.), Nigella (Nigella sativa L.), Laurel (Lauris nobilis), Karabaş (Lavandula stoechas), and Zahter (Thymbra spicata L. var. Spicata) against Covid-19 were investigated in vitro conditions. The six plants were evaluated for cytotoxic effect on Vero cells and determining inhibition of viral replication in Vero-E6 cells at concentrations of broad-spectrum antiviral non-cytotoxic against Covid-19 in cell culture and an additional antiviral effect against Covid-19. According to the results, the five examined plants (Saffron, Nigella, Laurel, Karabaş, Zahter) were ineffective against Covid-19 in vitro conditions. Interisingly, the water extract obtained from the root of the licorice plant (Glycyrrhiza glabra) inhibited Covid-19 in vitro conditions in the 2nd dilution (1: 4) following the initial concentration in Vero-E6 cells.


2021 ◽  
Author(s):  
Dong-Kyun Ryu ◽  
Hye-Min Woo ◽  
Bobin Kang ◽  
Hanmi Noh ◽  
Jong-In Kim ◽  
...  

The Delta variant originally from India is rapidly spreading across the world and causes to resurge infections of SARS-CoV-2. We previously reported that CT-P59 presented its in vivo potency against Beta and Gamma variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on the Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal study. CT-P59 showed reduced antiviral activity but enabled neutralization against Delta, Epsilon, and Kappa variants in cells. In line with in vitro results, the mouse challenge experiment with the Delta variant substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against the Delta variant infection, hinting that CT-P59 has therapeutic potency for patients infected with Delta and its associated variants.


2010 ◽  
Vol 54 (6) ◽  
pp. 2517-2524 ◽  
Author(s):  
Katrina Sleeman ◽  
Vasiliy P. Mishin ◽  
Varough M. Deyde ◽  
Yousuke Furuta ◽  
Alexander I. Klimov ◽  
...  

ABSTRACT Favipiravir (T-705) has previously been shown to have a potent antiviral effect against influenza virus and some other RNA viruses in both cell culture and in animal models. Currently, favipiravir is undergoing clinical evaluation for the treatment of influenza A and B virus infections. In this study, favipiravir was evaluated in vitro for its ability to inhibit the replication of a representative panel of seasonal influenza viruses, the 2009 A(H1N1) strains, and animal viruses with pandemic (pdm) potential (swine triple reassortants, H2N2, H4N2, avian H7N2, and avian H5N1), including viruses which are resistant to the currently licensed anti-influenza drugs. All viruses were tested in a plaque reduction assay with MDCK cells, and a subset was also tested in both yield reduction and focus inhibition (FI) assays. For the majority of viruses tested, favipiravir significantly inhibited plaque formation at 3.2 μM (0.5 μg/ml) (50% effective concentrations [EC50s] of 0.19 to 22.48 μM and 0.03 to 3.53 μg/ml), and for all viruses, with the exception of a single dually resistant 2009 A(H1N1) virus, complete inhibition of plaque formation was seen at 3.2 μM (0.5 μg/ml). Due to the 2009 pandemic and increased drug resistance in circulating seasonal influenza viruses, there is an urgent need for new drugs which target influenza. This study demonstrates that favipiravir inhibits in vitro replication of a wide range of influenza viruses, including those resistant to currently available drugs.


2015 ◽  
Vol 2015 ◽  
pp. 1-29 ◽  
Author(s):  
Ricardo Silva-Carvalho ◽  
Fátima Baltazar ◽  
Cristina Almeida-Aguiar

The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Severalin vitroandin vivostudies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins.


2021 ◽  
Author(s):  
Wei Jingchen ◽  
Lu Yunfei ◽  
Rui Ying ◽  
Zhu Xuanyu ◽  
He Songqing ◽  
...  

COVID-19 pneumonia has now spread widely in the world. Currently, no specific antiviral drugs are available. The vaccine is the most effective way to control the epidemic. Passive immune antibodies are also an effective method to prevent and cure COVID-19 pneumonia. We used the SARS-CoV-2 S receptor- binding domain (RBD) as an antigen to immunize layers in order to extract, separate, and purify SARS-CoV-2-IgY from egg yolk. SARS-CoV-2-IgY (S-IgY) can block the entry of SARS-CoV-2 into the Cells and reduce the viral load in cells. The Half effective concentration (EC50) of W3-IgY (S-IgY in the third week after immunization) is 1.35 plusm 0.15nM. The EC50 of W9-IgY (S-IgY in the ninth week after immunization) is 2.76 plusm 1.54 nM. When the dose of S-IgY is 55 nM, the fluorescence representing intracellular viral protein is obviously weakened in Immunofluorescence microscopy. Results of Sars-CoV-2 /Vero E6 cell experiment confirmed that S-IgY has a strong antiviral effect on SARS-CoV-2, and its (EC50) is 27.78 plusm1.54 nMvs 3,259 plusm 159.62 nM of Redesivir (differ ﹥106 times P<0.001 ). S-IgY can inhibit the entry and replication of SARS-CoV-2, which is related to its targeting the ACE2 binding domain. S-IgY is safe, efficient, stable, and easy to obtain. This antibody can be an effective tool for preventing and treating COVID-19 pneumonia.


2021 ◽  
Vol 7 (2) ◽  
pp. 95-98
Author(s):  
Zakia Jahan ◽  
Masudul Hassan

The Coronavirus disease 2019 (COVID-19) outbreak, forcing us to face unprecedented moments in the world. The huge devastating impact of the world due to the covid-19 attack causes the brink of no return. However, there is no proven and specific treatment for Covid -19. Very few medications have received Emergency Use of Authorization. A recent in vitro study was the first time to find out and to assess the antiviral effect of Ivermectin on COVID-19. The study showed that Ivermectin was active against COVID- 19-infected cells, was able to kill effectively almost all viral particles within 48 h. In these moments of crisis, FDA-approved ivermectin is a ray of hope. Bangladesh Journal of Infectious Diseases 2020;7(2):95-98


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