Antiviral Substances Research Articles

MONARDA FISTULOSA L. FROM THE FOREST-STEPPE ZONE OF WESTERN SIBERIA: ANTI-INFLUENZA ACTIVITY OF PLANT COMPONENTS DURING THE VEGETATION PERIOD

This is a study on antiviral activity of various extracts from the plant Monarda fistulosa L. cultivated in the forest-steppe zone of Western Siberia during the vegetation period. The activity of aqueous and aqueous-ethanolic extracts of M. fistulosa during the whole vegetation period and two polyphenolic fractions from this plant at the flowering stage was investigated against human influenza virus A/Aichi/2/68 (H3N2) and avian influenza virus A/chicken/Kurgan/05/2005 (H5N1). The anti-influenza activity was compared among the extracts and the polyphenolic fractions from M. fistulosa at the flowering stage. It was shown that antiviral activity against each subtype of the influenza A virus differed throughout the entire vegetation period, depending on the developmental stage of M. fistulosa and the type of extraction. Influenza virus A/Aichi/2/68 (H3N2) infectivity was most strongly inhibited by aqueous-ethanolic extracts from M. fistulosa raw material collected at the growth stage and by the aqueous extract from the fruiting initiation stage. Inhibition of the infectivity of influenza virus A/chicken/Kurgan/05/2005 (H5N1) was achieved by one or another M. fistulosa extract almost throughout the whole vegetation period. It is found that Polyphenolic Fractions 1 and 2 are more active against influenza virus A/Aichi/2/68 (H3N2), but aqueous and aqueous-ethanolic extracts are more active against influenza virus A/chicken/Kurgan/05/2005 (H5N1). On the condition of further in-depth studies, our experimental data suggest that M. fistulosa plant components can be recommended as medicinal (antiviral) substances against influenza viruses A/Aichi/2/68 (H3N2) and A/chicken/Kurgan/05/2005 (H5N1).

MONARDA FISTULOSA L. FROM THE FOREST-STEPPE ZONE OF WESTERN SIBERIA: ANTI-INFLUENZA ACTIVITY OF PLANT COMPONENTS DURING THE VEGETATION PERIOD

This is a study on antiviral activity of various extracts from the plant Monarda fistulosa L. cultivated in the forest-steppe zone of Western Siberia during the vegetation period. The activity of aqueous and aqueous-ethanolic extracts of M. fistulosa during the whole vegetation period and two polyphenolic fractions from this plant at the flowering stage was investigated against human influenza virus A/Aichi/2/68 (H3N2) and avian influenza virus A/chicken/Kurgan/05/2005 (H5N1). The anti-influenza activity was compared among the extracts and the polyphenolic fractions from M. fistulosa at the flowering stage. It was shown that antiviral activity against each subtype of the influenza A virus differed throughout the entire vegetation period, depending on the developmental stage of M. fistulosa and the type of extraction. Influenza virus A/Aichi/2/68 (H3N2) infectivity was most strongly inhibited by aqueous-ethanolic extracts from M. fistulosa raw material collected at the growth stage and by the aqueous extract from the fruiting initiation stage. Inhibition of the infectivity of influenza virus A/chicken/Kurgan/05/2005 (H5N1) was achieved by one or another M. fistulosa extract almost throughout the whole vegetation period. It is found that Polyphenolic Fractions 1 and 2 are more active against influenza virus A/Aichi/2/68 (H3N2), but aqueous and aqueous-ethanolic extracts are more active against influenza virus A/chicken/Kurgan/05/2005 (H5N1). On the condition of further in-depth studies, our experimental data suggest that M. fistulosa plant components can be recommended as medicinal (antiviral) substances against influenza viruses A/Aichi/2/68 (H3N2) and A/chicken/Kurgan/05/2005 (H5N1).

Establishment of sheep nasal mucosa explant model and its application in antiviral research.

The nasal mucosa is the first barrier to pathogen invasion through the respiratory tract. Few studies have focused on nasal resistance to invasion by respiratory pathogens due to the lack of models related to the nasal mucosa. Hence, it is necessary to construct a nasal mucosal model to study host-pathogen interactions. We established a long-term in vitro sheep nasal mucosa explant model (NMEM), which exhibited typical epithelial cilia and epithelial proliferation ability within 11 days. Moreover, to evaluate whether the NMEM was suited for in vitro pathogenic study, we used pseudorabies virus (PRV) and showed that it successfully infected and produced severe lesions in the NMEM, particularly interferon (IFN)-stimulated gene product 15 (ISG15). IFN decreased significantly after the PRV infection. Similarly, we used this NMEM model to screen several antiviral substances, such as probiotics and drugs. A previous study showed that nasal commensal bacteria, particularly Bacillus subtilis, had high antiviral activity. Then, we used the NMEM to evaluate six sheep-derived B. subtilis strains and demonstrated that it significantly induced the production of IFN and expression of ISG15. The sheep-derived B. subtilis was pretreated with the sheep NMEM before the PRV infection to evaluate the antiviral effect. The results showed that NSV2 significantly inhibited infection by PRV and reduced the viral load (p < 0.05). Furthermore, NSV2 may inhibit PRV replication by enhancing ISGylation of cells. In conclusion, we established a reliable in vitro culture model of sheep NMEM, and applied it in antiviral research.

Investigation of antiviral substances in Covid 19 by Molecular Docking: In Silico Study.

This paper aimed to investigate the antiviral drugs against Sars-Cov-2 main protease (MPro) using in silico methods. A search was made for antiviral drugs in the PubChem database and antiviral drugs such as Bictegravir, Emtricitabine, Entecavir, Lamivudine, Tenofovir, Favipiravir, Hydroxychloroquine, Lopinavir, Oseltamavir, Remdevisir, Ribavirin, Ritonavir were included in our study. The protein structure of Sars-Cov-2 Mpro (PDB ID: 6LU7) was taken from the Protein Data Bank (www.rcsb. Org) system and included in our study. Molecular docking was performed using AutoDock/Vina, a computational docking program. Protein-ligand interactions were performed with the AutoDock Vina program. 3D visualizations were made with the Discovery Studio 2020 program. N3 inhibitor method was used for our validation. In the present study, bictegravir, remdevisir and lopinavir compounds in the Sars-Cov-2 Mpro structure showed higher binding affinity compared to the antiviral compounds N3 inhibitor, according to our molecular insertion results. However, the favipiravir, emtricitabine and lamuvidune compounds were detected very low binding affinity. Other antiviral compounds were found close binding affinity with the N3 inhibitor. Bictegravir, remdevisir and lopinavir drugs showed very good results compared to the N3 inhibitor. Therefore, they could be inhibitory in the Sars Cov-2 Mpro target.

In vitro antiviral activity of persimmon-derived tannin against avian influenza viruses.

Tannins derived from natural plant sources are known to provide many health benefits to humans and animals. Among the various tannins, those derived from persimmon (Diospyros kaki) have exhibited strong inactivating effects against pathogens that induce diseases in humans. However, few studies have focused on the antiviral effects of persimmon tannin against pathogen-induced diseases in animals. In this study, we investigated the antiviral effects of persimmon tannin against various avian influenza viruses revealing that tannin at a concentration of 1.0mg ml-1 reduced viral infectivity in >6.0-log scale against all tested avian influenza viruses. In addition, this persimmon tannin concentration effectively inhibited the receptor binding and membrane fusion abilities of viral hemagglutinin (HA), which play important roles in avian influenza virus infection. These results suggest that persimmon tannin inactivates the HA of avian influenza viruses and reduces their infectivity. Persimmon tannin is a safer natural substance than the currently used chemical compound related to antiviral substance. When inactivation of the viruses which are present in environmental water such as roosting water of wild birds will be needed, persimmon tannin is expected to become an antiviral resource that may prevent the spread of several avian influenza virus subtypes.

GC/MS Analysis, Cytotoxicity, and Antiviral Activities of Annona glabra Hexane Extract Supported by In Silico Study.

Annona glabra Linn is employed in conventional medicine to treat a number of human disorders, including cancer and viruses. In the present investigation, the significant phytochemical components of Annona glabra hexane extract were identified using gas chromatography-mass spectrometry (GC-MS) analysis. Three major compounds were identified in the hexane extract: tritriacontane (30.23%), 13, 17-dimethyl-tritriacontane (22.44%), and limonene (18.97%). MTT assay was used to assess the cytotoxicity of the extract on six human cancer cell lines including liver (HepG-2), pancreas (PANC-1), lung (A-549), breast (MCF-7, HTB-22), prostate (PC-3), and colon (CACO-2, ATB-37). The extract exhibited significant cytotoxic activity against both CACO-2 and A-549 cancer cell lines (IC50 = 47 ± 0.74 μg/mL and 56.82 ± 0.92 μg/mL) in comparison with doxorubicin (IC50 = 31.91 ± 0.81 μg/mL and 23.39 ± 0.43 μg/mL) and of SI of 3.8 and 3.1, respectively. It also induced moderate-to-weak activities against the other cancerous cell lines: PC-3, PANC-1, MCF-7, and HepG-2 (IC50 = 81.86 ± 3.26, 57.34 ± 0.77, 80.31 ± 4.13, and 57.01 ± 0.85 μg/mL) in comparison to doxorubicin (IC50 = 32.9 ± 1.74, 19.07 ± 0.2, 15.48 ± 0.84 and 5.4 ± 0.22 μg/mL, respectively) and SI of 2.2, 3.1, 2.2, and 3.1, respectively. In vitro anti-HSV1 (Herpes simplex 1 virus) and HAV (Hepatitis A virus) activity was evaluated using MTT colorimetric assay with three different protocols to test protective, anti-replicative, and anti-infective antiviral activities, and three separate replications of each experiment were conducted. The plant extract showed promising protective and virucidal activity against HSV1 with no significant difference with acyclovir (79.55 ± 1.67 vs. 68.44 ± 7.62 and 70.91 ± 7.02 vs. 83.76 ± 5.67), while it showed mild protective antiviral activity against HAV (48.08 ±3.46) with no significant difference vs. acyclovir (36.89 ± 6.61). The selected main compounds were examined for their bioactivity through in silico molecular docking, which exhibited that limonene could possess the strongest antiviral properties. These findings support Annona glabra's conventional use, which is an effective source of antiviral and anticancer substances that could be used in pharmaceuticals.

Review on the Antiviral Organic Agents against Fish Rhabdoviruses

Fish rhabdoviruses are harmful single-stranded RNA viruses with high mortality rates which cause considerable economic losses in aquaculture. It is imperative to explore and develop new antiviral compounds against them. In recent years, in addition to inorganic antiviral substances, more than 50 different organic compounds have been confirmed to be effective in the prevention and treatment of rhabdovirus infection and its dissemination in fish. The main types of extracts or agents and their trial designs are here considered for review. This review reveals the reported antiviral activities of extracts from organisms, proteins, lipids, polysaccharides, nucleic acids, coumarin derivatives, arctigenin derivatives, and other antiviral organic molecules against fish rhabdoviruses, respectively. Additionally, their antiviral mechanisms of action include direct virucidal effects, inhibiting virus-induced host cell apoptosis, the blocking of the viral replication cycle, affecting gene expression and innate antiviral immune responses, and so on. This review also gives perspectives on how to comprehensively explore the potential applications of the candidate molecules, which lay the foundation for the future development of new compounds or strategies for the prevention and control of fish rhabdoviruses in aquaculture.

Preclinical development of kinetin as a safe error-prone SARS-CoV-2 antiviral able to attenuate virus-induced inflammation

Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activity are highly desirable. We identified here that kinetin (MB-905) inhibits the in vitro replication of SARS-CoV-2 in human hepatic and pulmonary cell lines. On infected monocytes, MB-905 reduced virus replication, IL-6 and TNFα levels. MB-905 is converted into its triphosphate nucleotide to inhibit viral RNA synthesis and induce error-prone virus replication. Coinhibition of SARS-CoV-2 exonuclease, a proofreading enzyme that corrects erroneously incorporated nucleotides during viral RNA replication, potentiated the inhibitory effect of MB-905. MB-905 shows good oral absorption, its metabolites are stable, achieving long-lasting plasma and lung concentrations, and this drug is not mutagenic nor cardiotoxic in acute and chronic treatments. SARS-CoV-2-infected hACE-mice and hamsters treated with MB-905 show decreased viral replication, lung necrosis, hemorrhage and inflammation. Because kinetin is clinically investigated for a rare genetic disease at regimens beyond the predicted concentrations of antiviral/anti-inflammatory inhibition, our investigation suggests the opportunity for the rapid clinical development of a new antiviral substance for the treatment of COVID-19.

Development and Validation of New Methods for Quality Control of the Antiviral Substance FAVIPIRAVIR

The introduction into the production of medicinal substances involves the creation of a pharmaceutical dossier, an important component of which is data on pharmaceutical development and quality control methods. The physico-chemical properties of the antiviral substance of favipiravir were investigated, and some basic sections of the analytical documentation were developed. With the help of a complex of physical, chemical, and physico-chemical methods of analysis, the "Identification" test was developed, and the structure of favipiravir was proven. Methods for the determination of related substances by the HPLC with UV detection and the assay of favipiravir by the acid-base titration method, suitable for substance quality control, have been developed. Relative retention times and correction factors for calculating their content are established for all impurities. The methods were validated on the parameters of specificity, accuracy, correctness, and linearity in the studied range of concentrations.

Feasibility and Efficacy of Romiplostim for the Treatment of Persistent Thrombocytopenia after Allogeneic Stem Cell Transplantation. a Single Centre Experience

Introduction. Persistent thrombocytopenia (PT) due to delayed primary platelet recovery or secondary graft failure with prolonged thrombocytopenia is a relevant and relatively common complication after allogeneic stem cell transplantation (alloSCT). It can result in transfusion dependence and hemorrhagic events, leading to increase of morbidity and mortality. Concomitant causes of PT after alloSCT are several and can include viral infections, graft-versus-host disease (GvHD), drug toxicity, thrombotic microangiopathy (TMA) and immune thrombocytopenia (ITP). Together with the treatment of the primary cause and the support with platelet transfusion, the use of thrombopoietin receptor agonists (TPO-RAs), which proved to be effective in several scenarios (e.g. ITP or aplastic anemia), is gaining a fundamental role also in the post alloSCT setting. To date, the use of TPO-RAs after transplant has been investigated in small studies or case reports. In this study, we evaluated the use of romiplostim in a larger patient cohort to determine its safety, efficacy and potential predictors of response. Materials and methods. We conducted a retrospective study on consecutive patients undergoing alloSCT and receiving romiplostim for the treatment of PT at the bone marrow transplantation unit of the University Hospital of Ulm. PT was defined as a platelet count < 20 Giga/l for 7 consecutive days after engraftment, the need for continuous transfusion during the post-transplant follow-up or a not rapidly reversible decrease of >50% of the platelet count not due to relapse of underlying hematological disease. Response to treatment was defined as a platelet count >50 Giga/l for at least 7 consecutive days without transfusion. Patients with residual bone marrow involvement of primary hematological disease were excluded. Univariate analysis was conducted using Fisher's exact test or Mann-Whitney-U-test. Results. Between 01/2019 and 12/2021 we identified a total of 119 out of 255 transplanted patients (46,7%) with PT receiving, as a part of the treatment, romiplostim during the post-transplant follow-up. Patient characteristics are listed in Table 1. The median platelet count at baseline was 32 Giga/l (r = 0 - 88). We started with romiplostim 250μg on a weekly basis, in 46,2% of cases the dose was escalated to 500 µg during treatment. Seventy-three percent showed a clinical response to treatment with a median time to response of 40 days (r = 7 - 565). We observed adverse events like thrombosis, pain syndrome, dizziness in only 8,4% of patients. The median duration of treatment was 168 days (r = 18 - 761). In patients with response, the median platelet count was 91 Giga/l (r = 53 - 212). In univariate analysis, we evaluated potential risk factors associated with poor response to romiplostim. While the presence of a viral reactivation (like CMV, EBV, BKV, HSV1) requiring systemic treatment was associated with a significant lower response rate (47.6% versus 79.6%, respectively for patients with or without reactivation, p= 0.005), the presence of active GvHD (also in case of steroid-refractory (SR) forms), of TMA and the number of CD34-positive stem cells of the graft did not play a role in determining the efficacy of romiplostim. We also evaluated the influence of graft cryopreservation, which was performed increasingly during the SARS-CoV-2 pandemic, on the rate of efficacy of romiplostim in PT treatment. We could not identify a significant difference as compared to the non-cryopreserved grafts. Conclusion. Our results indicate that romiplostim is overall well tolerated and represents a reasonable and effective treatment for PT after alloSCT. We observed that viral infections requiring systemic antiviral treatment could represent a predictor of worse response, which could potentially be explained by the myelotoxicity induced not only by the virus itself but also as a consequence of antiviral substances. Of note, especially considering that SR GvHD or TMA did not seem to impair the efficacy of romiplostim, the stimulation of TPO receptor could play a role in reducing the rate of morbidity and mortality associated with such severe complications of the post transplant follow-up. Also, cryopreservation did not impact on the rate of success of TPO-RAs based treatment strategy. These preliminary results need to be further validated in larger and prospective cohorts. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Characterization of L-Lysine-A-Oxidase, A New Antitumor And Antiviral Drug Substance Synthesized By Trichoderma

The trigger to the studies of L-lysine-a -oxidase is of great interest for the scientists across the world. Regarding Russian Federation, the enzyme is under examination by several laboratories. Attracted by the polyfunctionality of the enzyme, the likelihood of utilizing this substance in the creation of multiple dosage forms of different therapeutic orientation. Thus, the main aim of the study is to analyze the new characteristics of L-lysine-a -oxidase as a new antitumor and antiviral drug substance synthesized by Trichoderma. To meet the study’s aim, a biological experiments were carried out on guinea pigs weighing 200-250 g and CBA mice (CBA x C57BI) weighing 18-20 g, C57 Bl, SHR.Native L-lysine-a -oxidase was injected into C57BI mice five times intravenously at a dose of 35 U/kg. Blood was sampled every week for four weeks from the beginning of immunization (n=7), and the obtained sera of mice were analyzed by enzyme-linked immunosorbent assay according to a previously developed method. The sera were titrated in increments of 2. Tests of L-lysine-a -oxidase in mice and guinea pigs found low immunogenicity of Llysine- a -oxidase when administered in mice at a dose of 35 U/kg, or 0.8 ml of protein/kg. Based on the results obtained, antibodies not only reduce its catalytic activity but also affect the affinity of the enzyme with the substrate. Experiments on guinea pigs have shown that native and modified L-lysine-a -oxidase at a dose of 35 U/kg in vivo and in vitro has a low allergenic activity. The allergenic activity of L-lysine-a -oxidase was investigated in comparison with other drugs. The results od this article, can be considered as one of a brand-new and effective methods for assessing the body sensitization caused by the use of enzymes and can contribute to the development of the respective field.

Promising COVID-19 therapies on examples of some antiviral, immunomodulatory and natural substances use - review

COVID-19 is one of the biggest challenges to medicine ever. Because of its dissemination in population effective drug to cure it was needed. There were some trials on antiviral drugs like lopiravir/ritonavir, remdesivir, darunavir/cobicistat, favipiravir, molnupiravir, discovered originally in order to treat other diseases. Only remdesivir and molnupiravir seem to be beneficial for patients with COVID-19, both of them are approved in therapy in a large number of countries allover the world. [2]&#x0D; Another very important group of drugs used in trials against COVID-19 was immunomodulatory drugs. Some of them, like chloroquine/hydrochloroquine was very promising, but finally there were no evidences of its benefits found. [2] Corticosteroids used in moderate and severe COVID-19 caused general improvement of clinical status and decreased mortality. Interesting and quite promising may be use of interferons but for now lack of evidences does not allow to make clear statement about its benefits.&#x0D; There are some argumentations for natural methods of COVID-19 treatment. Dietary recommendations, vitamin and microelements supplementation may be helpful in the therapy and in addition may not have any adverse effects. Also, herbal mixtures, developed centuries ago in China found usage during COVID-19 pandemic. After analysis of thousands of cases Traditional Chinese Medicine can be considered as one of the most successful attempt in combating COVID-19. [6]

Low molecular weight chitooligosaccharide inhibits infection of SARS-CoV-2 in vitro.

AimsThe discovery of antiviral substances to respond to COVID‐19 is a global issue, including the field of drug development based on natural materials. Here, we showed that chitosan‐based substances have natural antiviral properties against SARS‐CoV‐2 in vitro.Methods and ResultsThe molecular weight of chitosan‐based substances was measured by the gel permeation chromatography analysis. In MTT assay, the chitosan‐based substances have low cytotoxicity to Vero cells. The antiviral effect of these substances was confirmed by quantitative viral RNA targeting the RdRp and E genes and plaque assay. Among the substances tested, low molecular weight chitooligosaccharide decreased the fluorescence intensity of SARS‐CoV‐2 nucleocapsid protein of the virus‐infected cells in a dose‐dependent manner.ConclusionsIn conclusion, the chitooligosaccharide, a candidate for natural treatment, has antiviral effects against the SARS‐CoV‐2 virus in vitro.Significance and Impact of StudyIn this study, it was suggested for the first time that chitosan‐based substances such as chitooligosaccharide can have an antiviral effect on SARS‐CoV‐2 in vitro.

Antiviral Properties of Cerium Nanoparticles

According to the results of the study, the threshold limit values (TLVs) of CeO2, and Ce nanoparticles (NPs) for the culture of swine kidney embryonic cell line (SKECL) have been estimated. The TLVs are 0.1 &mu;g/cm3 for Ce NPs, and 1 &mu;g/cm3 for CeO2 NPs. All NPs were non-toxic for white mice at concentration of 2000 mg/kg, which opens up a perspective for the further use of these NPs in the development of antiviral substances. CeO2, and Ce NPs have decreased the titer of Teschovirus by 1.46-2 lg10 TCD50/ cm3 at TLVs at all stages of virus reproduction. Sensitivity of the strain Dniprovskyi-34 of species Teschovirus A, serotype Porcine teschovirus 1 (PTV-1), to solvents, proteolytic enzyme trypsin under the presence of CeO2, and Ce NPs has been studied. Under the presence of solvents, and trypsin, NPs decreased the infectious titer of the virus slightly by only 0.23 lg10 TCD50/cm3. CeO2, and Ce NPs have not shown antiviral activity under heating to 50 °C, either with the addition of 1 M solution of MgCl2 or without it, and did not cause significant decrease of infectious activity of the virus under pH values 2.0, 7.2, and 11.0 within 10 minutes exposition. Ability of CeO2, and Ce NPs to interact with viral particles, change their morphology, which can affect infective activity of the virus significantly, has been shown. Addition of CeO2, and Ce NPs to the antigen has caused the decrease of the titer of virus-neutralizing antibodies, though it remained high. The results of the studies can be used in development of disinfectants, and antiviral drugs.

A Satellite dsRNA Attenuates the Induction of Helper Virus-Mediated Symptoms in Aspergillus flavus.

Aspergillus flavus is an important fungal pathogen of animals and plants. Previously, we reported a novel partitivirus, Aspergillus flavus partitivirus 1 (AfPV1), infecting A. flavus. In this study, we obtained a small double-stranded (ds) RNA segment (734 bp), which is a satellite RNA of the helper virus, AfPV1. The presence of AfPV1 altered the colony morphology, decreased the number of conidiophores, created significantly larger vacuoles, and caused more sensitivity to osmotic, oxidative, and UV stresses in A. flavus, but the small RNA segment could attenuate the above symptoms caused by the helper virus AfPV1 in A. flavus. Moreover, AfPV1 infection reduced the pathogenicity of A. flavus in corn (Zea mays), honeycomb moth (Galleria mellonella), mice (Mus musculus), and the adhesion of conidia to host epithelial cells, and increased conidial death by macrophages. However, the small RNA segment could also attenuate the above symptoms caused by the helper virus AfPV1 in A. flavus, perhaps by reducing the genomic accumulation of the helper virus AfPV1 in A. flavus. We used this model to investigate transcriptional genes regulated by AfPV1 and the small RNA segment in A. flavus, and their role in generating different phenotypes. We found that the pathways of the genes regulated by AfPV1 in its host were similar to those of retroviral viruses. Therefore, some pathways may be of benefit to non-retroviral viral integration or endogenization into the genomes of its host. Moreover, some potential antiviral substances were also found in A. flavus using this system.

Endophytic Fungi as a Source of Antiviral Compounds - A Review.

Endophytic fungi are a rich source of secondary metabolites. The interactions between endophytes and their hosts lead to the production of several bioactive substances grouped into different classes, each having a wide variety of effects against various pathogens. The metabolites obtained from these organisms include steroids, alkaloids, phenols, isocoumarins, xanthones, quinones, and terpenoids, among others. These substances are known to have antibiotic, antiparasitic, antifungal, and antiviral effects. This review summarizes secondary metabolites with antiviral effects produced by endophytic fungi and highlights the importance of research in developing novel antiviral substances. We demonstrate that endophytic fungi are a rich source of secondary metabolites that combat pathologies caused by viruses. Optimizing practical and biotechnological screening tools for the research of these metabolites will provide promising drugs to combat these infections.

Second-Order Scattering Quenching in Fluorescence Spectra of Natural Humates as a Tracer of Formation Stable Supramolecular System for the Delivery of Poorly Soluble Antiviral Drugs on the Example of Mangiferin and Favipiravir.

In the present work, the methods of dynamic light scattering and fluorescence spectroscopy were applied to study the optical properties of aqueous dilutions of the humic substances complex (HC) as a potential drug delivery system. The supramolecular structures in the humate solution were characterized as monodisperse systems of the submicron range with a tendency to decrease in particle size with a decrease in the dry matter concentration. The slightly alkaline medium (8.3) of the studied aqueous dilutions of HC causes the absence of a pronounced fluorescence maximum in the region from 400 to 500 nm. However, the presence of an analytically significant, inversely proportional to the concentration second-order scattering (SOS) signal at 2λex = λem was shown. In the examples of the antiviral substances mangiferin and favipiravir, it was shown that the use of the humic complex as a drug carrier makes it possible to increase the solubility by several times and simultaneously obtain a system with a smaller particle size of the dispersed phase. It has been shown that HC can interact with mangiferin and favipiravir to form stable structures, which lead to a significant decrease in SOS intensities on HC SOS spectra. The scattering wavelengths, λex/λem, were registered at 350 nm/750 nm for mangiferin and 365 nm/730 nm for favipiravir, respectively. The increments of the scattering intensities (I0/I) turned out to be proportional to the concentration of antiviral components in a certain range of concentrations.

Biological activity of kencur (Kaempferia galanga L.) against SARS-CoV-2 main protease

COVID-19 is a syndrome affecting pulmonary function but rather in serious conditions leads to death. Kencur (Kaempferia galanga L.) is a type of rhizome plant in Indonesia that is used as an herbal medicine called Jamu because it is believed to be able to cure various types of diseases. One of which is for anti-virus. The goal of this study was to see how effective the compounds in kencur are against COVID-19 with a molecular docking strategy. Kencur biological activities were obtained from the library and the design of the Acute Respiratory Syndrome Main protease (Mpro) has been gained from the protein data bank website. In addition, the biological activities in kencur were examined utilizing Lipinski's five-point concept was used to evaluate their substance molecular characteristics. Molecular docking analysis was performed with the PyRx Virtual Screening Tool software. The PyRx program was used for molecular docking simulation. While, the Discovery Studio Visualizer program was used to visualize the interaction between SARS-CoV-2 (Mpro) and the pharmacologically active metabolites in kencur. The docking evaluation on three antiviral substances revealed that Quercetin had the lowest binding energy when bound with Mpro and thus had the greatest potential as a viral inhibitor.

Algal Metabolites Can Be an Immune Booster against COVID-19 Pandemic.

The world has faced the challenges of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for the last two years, first diagnosed at the end of 2019 in Wuhan and widely distributed worldwide. As a result, the WHO has proclaimed the illness brought on by this virus to be a global pandemic. To combat COVID-19, researcher communities continuously develop and implement rapid diagnoses, safe and effective vaccinations and other alternative therapeutic procedures. However, synthetic drug-related side effects and high costs have piqued scientists’ interest in natural product-based therapies and medicines. In this regard, antiviral substances derived from natural resources and some medicines have seen a boom in popularity. For instance, algae are a rich source of compounds such as lectins and sulfated polysaccharides, which have potent antiviral and immunity-boosting properties. Moreover, Algae-derived compounds or metabolites can be used as antibodies and vaccine raw materials against COVID-19. Furthermore, some algal species can boost immunity, reduce viral activity in humans and be recommended for usage as a COVID-19 preventative measure. However, this field of study is still in its early stages of development. Therefore, this review addresses critical characteristics of algal metabolites, their antioxidant potential and therapeutic potential in COVID-19.

Epidemiology, Transmission, Clinical Features, Diagnosis, Treatment, and Prevention of COVID19: An Updated Review

Introduction: The novel coronavirus disease of 2019 (COVID-19) appeared almost two years ago in China and quickly created a pandemic and affected all aspects of human life. The virus, termed SARS-CoV-2, is generally asymptomatic but contagious and might have originated from bats. Nowadays, the mechanisms underlying the infection and the incidence of SARS-CoV-2 are distinguishable from previous coronaviruses. Early diagnosis and supportive treatment are necessary to cure the patients with COVID-19. Early evidence recommended that children are just likely as adults to become infected with this novel virus. It is now established that children are more often show gastrointestinal manifestations than adults do, and many children affected by SARS-CoV-2 are asymptomatic. Over 300 vaccine projects are recently developed by the scientific community to treat COVID-19 disease; however, these vaccines might lose efficacy by a number of unpredicted issues, including the emergence of new SARS-CoV-2 mutants. Conclusion: Due to the high prevalence and worldwide widespread of COVID-19, many studies are underway to find treatment modalities and develop new vaccines or antiviral substances to fight the virus. The COVID-19 pandemic is not only a challenge to global health but also has globally affected mental, social, and economic health. Moreover, the post-corona pandemic condition will undoubtedly have many Socioeconomic Challenges. This review study has been focused on epidemiology, virology, transmission methods, clinical features, laboratory findings, and prevalent mutations of the SARS-CoV-2 virus. We hope that information provided within this article will significantly benefit researchers currently investigating COVID-19 patients.