Plant-Based Natural Products and Extracts: Potential Source to Develop New Antiviral Drug Candidates.

Viral infections are among the most complex medical problems and have been a major threat to the economy and global health. Several epidemics and pandemics have occurred due to viruses, which has led to a significant increase in mortality and morbidity rates. Natural products have always been an inspiration and source for new drug development because of their various uses. Among all-natural sources, plant sources are the most dominant for the discovery of new therapeutic agents due to their chemical and structural diversity. Despite the traditional use and potential source for drug development, natural products have gained little attention from large pharmaceutical industries. Several plant extracts and isolated compounds have been extensively studied and explored for antiviral properties against different strains of viruses. In this review, we have compiled antiviral plant extracts and natural products isolated from plants reported since 2015.

Research progress of epigallocatechin-3-gallate (EGCG) on anti-pathogenic microbes and immune regulation activities.

At the end of 2019, the COVID-19 virus spread worldwide, infecting millions of people. Infectious diseases induced by pathogenic microorganisms such as the influenza virus, hepatitis virus, and Mycobacterium tuberculosis are also a major threat to public health. The high mortality caused by infectious pathogenic microorganisms is due to their strong virulence, which leads to the excessive counterattack by the host immune system and severe inflammatory damage of the immune system. This paper reviews the efficacy, mechanism and related immune regulation of epigallocatechin-3-gallate (EGCG) as an anti-pathogenic microorganism drug. EGCG mainly shows both direct and indirect anti-infection effects. EGCG directly inhibits early infection by interfering with the adsorption on host cells, inhibiting virus replication and reducing bacterial biofilm formation and toxin release; EGCG indirectly inhibits infection by regulating immune inflammation and antioxidation. At the same time, we reviewed the bioavailability and safety of EGCG in vivo. At present, the bioavailability of EGCG can be improved to some extent using nanostructured drug delivery systems and molecular modification technology in combination with other drugs. This study provides a theoretical basis for the development of EGCG as an adjuvant drug for anti-pathogenic microorganisms.

Developments in antiviral drug design, discovery and development in 2004.

This article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. Important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis B, hepatitis C; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus and human cytomegalovirus; the respiratory viruses, influenza, respiratory syncytial virus, human metapneumovirus, picornaviruses, measles and the severe acute respiratory syndrome coronavirus; human papilloma virus; rotavirus; Ebola virus and West Nile virus, are reviewed.

Resistance of hepatitis B virus to antiviral drugs: current aspects and directions for future investigation.

Despite the existence of vaccines, chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. Interferon therapy successfully controls infection in only a small percentage of chronically infected individuals. The recent approval of the nucleoside analogue lamivudine for the treatment of chronic HBV infection has ushered in a new era of antiviral therapy. While lamivudine is highly effective at controlling viral infection short-term, prolonged therapy has been associated with an increasing incidence of viral resistance. Thus, it appears that lamivudine alone will not be sufficient to control chronic viral infection in the majority of individuals. In addition to lamivudine, several new nucleoside and nucleotide analogues that show promising antihepadnaviral activity are in various stages of development. Lamivudine resistance has been found to confer cross-resistance to some of these compounds and it is likely that resistance to newer antivirals may also develop during prolonged use. Drug resistance therefore poses a major threat to nucleoside analogue-based therapies for chronic HBV infection. Fortunately, combination chemotherapy (antiviral therapy with two or more agents) can minimize the chance that resistance will develop and can be expected to achieve sustained reductions in viral load, provided that suitable combinations of agents are chosen. Here we review the basis of drug resistance in HBV, with emphasis on aspects that are likely to affect drug choice in future.

The use of tri(n-butyl)phosphate detergent mixtures to inactivate hepatitis viruses and human immunodeficiency virus in plasma and plasma's subsequent fractionation.

The treatment of plasma with organic solvent/detergent mixtures at the time of plasma collection or pooling could reduce the exposure of technical staff to infectious viruses and enhance the viral safety of the final product. Treatment of plasma for 4 hours with 2-percent tri(n-butyl)phosphate (TNBP) at 37 degrees C, with 1-percent TNBP and 1-percent polyoxyethylensorbitan monooleate (Tween 80) at 30 degrees C, or with 1-percent TNBP and 1-percent polyoxyethylene ethers, (Triton X-45) at 30 degrees C resulted in the rapid and complete inactivation of greater than or equal to 10(4) tissue culture-infectious doses (TCID50) of vesicular stomatitis and Sindbis viruses, which are used as surrogates. Treatment of plasma with TNBP and TNBP and Tween-80 was shown to inactivate greater than or equal to 10(4) TCID50 of human immunodeficiency virus. TNBP treatment of plasma contaminated with 10(6) chimpanzee-infectious doses (CID50) of hepatitis B virus and 10(5) CID50 of non-A,non-B hepatitis virus prevented the transmission of hepatitis to chimpanzees. Immediately after treatment of plasma with 2-percent TNBP, the recovery of factors VIII, IX, and V and antithrombin III was 80, 90, 40, and 100 percent, respectively. Recovery of all factors was greater than or equal to 90 percent after treatment with TNBP and detergent mixtures. Treated plasma was fractionated by standard techniques into antihemophilic factor and prothrombin complex concentrates, immune globulin, and albumin. Prior treatment with TNBP or TNBP and detergent did not affect the separations of desired proteins. Therefore, it appears possible to inactivate viruses in plasma before the execution of standard fractionation procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Photochemical decontamination of blood components containing hepatitis B and non-A, non-B virus.

Diluted plasma samples containing 10(2), 10(3), 10(4), and 10(5) chimpanzee infectious doses (CID) of a human non-A, non-B hepatitis virus (NANBV) were treated with a combination of two psoralen compounds, 4'-aminomethyl-4,5',8-trimethylpsoralen and 4,5',8-trimethylpsoralen, and exposed to long wavelength ultraviolet. Each dilution was then transfused into one of four chimpanzees. In a second experiment, three samples containing 10(4.5) CID of hepatitis B virus (HBV) and two samples containing 10(4) CID of NANBV were treated with 8-methoxypsoralen (8-MOP) and ultraviolet irradiation. Two chimpanzees were each transfused with both a treated HBV and a treated NANBV sample. The third chimpanzee was inoculated with a treated HBV sample alone. In the six months after inoculation none of the animals showed biochemical or histological evidence of hepatitis. In experiments involving NANBV inocula, the susceptibility of the animals was confirmed by subsequent challenge with untreated NANBV. Factor VIII concentrate containing virus and photochemically treated as in the first experiment retained an average of 91% of its activity while that in the second experiment retained 94% of its activity.

Inactivation of the Hutchinson strain of hepatitis non-A, non-B virus in intravenous immunoglobulin by beta-propiolactone.

beta-propiolactone (beta-PL) treatment has been evaluated for its ability to inactivate 10(3.5) chimpanzee infectious doses (CID50) of the Hutchinson strain of hepatitis non-A, non-B virus (HNANBV). Two chimpanzees were inoculated with a beta-PL-treated immunoglobulin solution to which this dose of the titrated virus had been added prior to beta-PL treatment. beta-PL treatment was performed in accordance with the production procedure used for a licensed intravenous immunoglobulin preparation. Neither animal developed hepatitis. When subsequently challenged with the same spiked immunoglobulin solution that had not been beta-PL treated, both animals developed clear-cut hepatitis non-A, non-B. The results of this experiment demonstrate that beta-PL treatment is effective for the inactivation of hepatitis non-A, non-B virus in intravenous immunoglobulin.

Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies.

An aqueous extract of the plant Phyllanthus niruri inhibits endogenous DNA polymerase of hepatitis B virus and binds to the surface antigen of hepatitis B virus in vitro. The extract also inhibits woodchuck hepatitis virus (WHV) DNA polymerase and binds to the surface antigen of WHV in vitro. The extract, nontoxic to mice, was tested for antiviral activity in woodchucks (Marmota monax). In a trial using six long-term WHV-carrier woodchucks, five treated animals showed a faster decrease in woodchuck hepatitis virus surface antigen titer compared to one untreated control. In animals recently infected with WHV, the extract was effective when administered i.p. in three out of four animals in reducing and within 3-6 weeks eliminating both the surface antigen titer and DNA polymerase activity in serum. The treatment was discontinued after 10 weeks, and the treated animals have remained free of detectable markers of WHV for more than 45 weeks. In contrast, three untreated controls remained positive for both markers for WHV. One of the controls died after 8 weeks; the other two controls have remained positive for WHV markers for more than 45 weeks. In a third trial with long-term carriers, test animals treated subcutaneously with the extract for 12 weeks did not respond; but on switching the mode of administration to i.p., two out of the five animals showed a significant decrease in woodchuck hepatitis virus surface antigen titer compared to controls.