Evidence that Ginkgo Biloba could use in the influenza and coronavirus COVID-19 infections.

Coronavirus COVID-19 pandemic invades the world. Public health evaluates the incidence of infections and death, which should be reduced and need desperately quarantines for infected individuals. This article review refers to the roles of Ginkgo Biloba to reduce the risk of infection in the respiratory tract, the details on the epidemiology of corona COVID-19 and influenza, and it highlights how the Ginko Biloba could have been used as a novel treatment.Ginkgo Biloba can reduce the risk of infection by several mechanisms; these mechanisms involve Ginkgo Biloba contains quercetin and other constituents, which have anti-inflammatory and immune modulator effects by reducing pro-inflammatory cytokines concentrations. Cytokines cause inflammation which have been induced the injuries in lung lining.Some observational studies confirmed that Ginkgo Biloba reduced the risk of asthma, sepsis and another respiratory disease as well as it reduced the risk of cigarette smoking on respiratory symptoms. While other evidences suggested the characters of Ginkgo Biloba as an antivirus agent through several mechanisms. Ginkgolic acid (GA) can inhibit the fusion and synthesis of viral proteins, thus, it inhibit the Herpes Simplex Virus type1 (HSV-1), genome replication in Human Cytomegalovirus (HCMV) and the infections of the Zika Virus (ZIKV). Also, it inhibits the wide spectrum of fusion by inhibiting the three types of proteins that have been induced fusion as (Influenza A Virus [IAV], Epstein Barr Virus [EBV], HIV and Ebola Virus [EBOV]).The secondary mechanism of GA targeting inhibition of the DNA and protein synthesis in virus, greatly have been related to its strong effects, even afterward the beginning of the infection, therefore, it potentially treats the acute viral contaminations like (Measles and Coronavirus COVID-19). Additionally, it has been used topically as an effective agent on vigorous lesions including (varicella-zoster virus [VZV], HSV-1 and HSV-2). Ginkgo Biloba may be useful for treating the infected people with coronavirus COVID-19 through its beneficial effect. To assess those recommendations should be conducted with random control trials and extensive population studies.

Bioactive Natural Antivirals: An Updated Review of the Available Plants and Isolated Molecules.

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.

Ultrasensitive Electrical Detection of Hemagglutinin for Point-of-Care Detection of Influenza Virus Based on a CMP-NANA Probe and Top-Down Processed Silicon Nanowire Field-Effect Transistors.

Rather than the internal genome nucleic acids, the biomolecules on the surface of the influenza virus itself should be detected for a more exact and rapid point-of-care yes/no decision for influenza virus-induced infectious diseases. This work demonstrates the ultrasensitive electrical detection of the HA1 domain of hemagglutinin (HA), a representative viral surface protein of the influenza virus, using the top-down complementary metal oxide semiconductor (CMOS) processed silicon nanowire (SiNW) field-effect transistor (FET) configuration. Cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-NANA) was employed as a probe that specifically binds both to the aldehyde self-aligned monolayer on the SiNWs and to HA1 simultaneously. CMP-NANA was serially combined with two kinds of linkers, namely 3-aminopropyltriethoxysilane and glutaraldehyde. The surface functionalization used was verified using the purification of glutathione S-transferase-tagged HA1, contact angle measurement, enzyme-linked immunosorbent assay test, and isoelectric focusing analysis. The proposed functionalized SiNW FET showed high sensitivities of the threshold voltage shift (ΔVT) ~51 mV/pH and the ΔVT = 112 mV (63 mV/decade) with an ultralow detectable range of 1 fM of target protein HA1.

The preventive and therapeutic potential of natural polyphenols on influenza.

Influenza virus belongs to orthomyxoviridae family. This virus is a major public health problems, with high rates of morbidity and mortality. Despite a wide range of pharmacotherapeutic choices inhibiting specific sequences of pathological process of influenza, developing more effective therapeutic options is an immediate challenge. In this paper, a comprehensively review of natural polyphenolic products used worldwide for the management of influenza infection is presented. Cellular and molecular mechanisms of the natural polyphenols on influenza infection including suppressing virus replication cycle, viral hemagglutination, viral adhesion and penetration into the host cells, also intracellular transductional signaling pathways have been discussed in detail. Based on cellular, animal, and human evidence obtained from several studies, the current paper demonstrates that natural polyphenolic compounds possess potential effects on both prevention and treatment of influenza, which can be used as adjuvant therapy with conventional chemical drugs for the management of influenza and its complications.

Roadblocks to translational challenges on viral pathogenesis.

Distinct roadblocks prevent translating basic findings in viral pathogenesis into therapies and implementing potential solutions in the clinic. An ongoing partnership between the Volkswagen Foundation and Nature Medicine resulted in an interactive meeting in 2012, as part of the "Herrenhausen Symposia" series. Current challenges for various fields of viral research were recognized and discussed with a goal in mind--to identify solutions and propose an agenda to address the translational barriers. Here, some of the researchers who participated at the meeting provide a concise outlook at the most pressing unmet research and clinical needs, identifying these key obstacles is a necessary step towards the prevention and cure of human viral diseases.

Anti-influenza virus activity of Ginkgo biloba leaf extracts.

We examined the influence of Ginkgo biloba leaf extract (EGb) on the infectivity of influenza viruses in Madin-Darby canine kidney (MDCK) cells. Plaque assays demonstrated that multiplication of influenza viruses after adsorption to host cells was not affected in the agarose overlay containing EGb. However, when the viruses were treated with EGb before exposure to cells, their infectivity was markedly reduced. In contrast, the inhibitory effect was not observed when MDCK cells were treated with EGb before infection with influenza viruses. Hemagglutination inhibition assays revealed that EGb interferes with the interaction between influenza viruses and erythrocytes. The inhibitory effect of EGb was observed against influenza A (H1N1 and H3N2) and influenza B viruses. These results suggest that EGb contains an anti-influenza virus substance(s) that directly affects influenza virus particles and disrupts the function of hemagglutinin in adsorption to host cells. In addition to the finding of the anti-influenza virus activity of EGb, our results demonstrated interesting and important insights into the screening system for anti-influenza virus activity. In general, the plaque assay using drug-containing agarose overlays is one of the most reliable methods for detection of antiviral activity. However, our results showed that EGb had no effects either on the number of plaques or on their sizes in the plaque assay. These findings suggest the existence of inhibitory activities against the influenza virus that were overlooked in past studies.

Ching-fang-pai-tu-san inhibits the release of influenza virus.

ETHNOPHARMACOLOGICAL RELEVANCE: Ching-fang-pai-tu-san (CFPTS) is a Chinese herbal decoction that is used as a cure for the common cold, fever, headache, and poor circulation. However, no previous studies have investigated the mode of action of CFPTS against influenza virus infections. To investigate the antiviral mechanism of CFPTS, we examined viral entry, transcription, translation, viral glycoprotein hemagglutinin (HA) transport, and budding of the influenza virus. MATERIALS AND METHODS: The antiviral activity of nontoxic concentrations of CFPTS against influenza virus A/WSN/33 was examined by assaying (neutralization assay) its inhibition of the virus-induced cytopathic effects. The mode of CFPTS action was first examined with a time-of-addition assay of synchronized infections, followed by monitoring HA transport by immunofluorescence microscopy. Viral endocytosis was evaluated with attachment and penetration assays. The inhibition of viral replication was measured by quantitative real-time PCR, immunoblotting, and immunofluorescence microscopy. We also performed assays related to the inhibition of viral entry, such as neuraminidase activity and hemagglutinin activity assays. RESULTS: Based on the inhibition of the virus-induced cytopathic effect in Madin-Darby canine kidney cells, the EC(50) of CFPTS was about 1.44 ± 0.22 mg/mL against influenza virus A/WSN/33. CFPTS displayed a broad spectrum of inhibitory activities against different strains of influenza A virus, as well as some enteroviruses. However, this extract proved less effective against clinical oseltamivir-resistant strains and influenza B viruses. CFPTS did not suppress viral RNA or protein synthesis. According to a time-of-addition assay, the antiviral mechanism of CFPTS may involve viral budding or intracellular viral glycoprotein transport. A plaque reduction assay showed that CFPTS reduced both the plaque size and plaque quantity. The intracellular transport of viral glycoprotein hemagglutinin was blocked by CFPTS by immunofluorescence microscopic analysis. Thus, it is possible that the antiviral mechanism of CFPTS might inhibit the assembly of progeny virions and/or their subsequent release. CONCLUSIONS: Our results give scientific support to the use of CFPTS in the treatment of influenza virus infections. CFPTS has potential utility in the management of seasonal pandemics of influenza virus infections, like other clinically available drugs.

Attenuation of influenza virus infectivity with herbal-marine compound (HESA-A): an in vitro study in MDCK cells.

BACKGROUND: The influenza virus is still one of the most important respiratory risks affecting humans which require effective treatments. In this case, traditional medications are of interest. HESA-A is an active natural biological compound from herbal-marine origin. Previous studies have reported that the therapeutic properties of HESA-A are able to treat psoriasis vulgaris and cancers. However, no antiviral properties have been reported. METHODS: This study was designed to investigate the potential antiviral properties of HESA-A and its effects in modulating TNF-α and IL-6 cytokine levels. HESA-A was prepared in normal saline as a stock solution (0.8 mg/ml, pH = 7.4). Percentages of cell survival when exposed to different concentrations of HESA-A at different time intervals was determined by MTT assay. To study the potential antiviral activity of HESA-A, Madin-Darby Canine Kidney (MDCK) cells were treated with the effective concentration (EC50) of HESA-A (0.025 mg/ml) and 100 TCID50/0.1 ml of virus sample under different types of exposure. RESULTS: Based on the MTT method and hemagglutination assay (HA), HESA-A is capable of improving cell viability to 31% and decreasing HA titre to almost 99% in co-penetration exposures. In addition, based on quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), it was found that HESA-A causes decrements in TNF-α and IL-6 cytokine expressions, which was significant for TNF-α (p ≤ 0.05) but not for IL-6. CONCLUSION: In conclusion, HESA-A was effective against influenza infection through suppressing cytokine expression.

[Influence of separate components of Yiqi Qingwen Jiedu mixture to serum inflammatory cytokines of mice infected with influenza virus FM1].

OBJECTIVE: To observe dynamically the influence of 4 parts of forming of YQJM (Yiqi Qingwen Jiedu mixture) (referred to as 4 parts of forming) including the methods of relieving superficies with acrid-warm, relieving superficies with acrid-cold, clearing away heat and poison and replenishing Qi to serum inflammatory cytokines of the model mice infected with influenza virus. And to discuss the mechanism of 4 parts of forming of anti-influenza immune injury and restoration. METHOD: Made the model with the mice infected by FM1 influenza infection, used ELISA method, observed dynamically the influence of four methods on the level of serum TNF-alpha, IL-6, IL-1, IFN-gamma and IL-10 inflammatory cytokines. RESULT: The level of serum TNF-alpha, IL-6, IL-1 and IFN-gamma of mice infected by FM1 significantly increased, while the level of serum IL-10 was lower than the control group on the first day of infection, but the levels were much higher than the control group in 3 to 7 days after infection. The method of relieving superficies with acrid-warm significantly decreased the levels of serum TNF-alpha, IL-6, IL-1 on the 5th day after infection, and significantly increased the levels of serum IL-10 on the 3rd and 7th day after infection. The method could inhibit the immune injury to some extent. The method of relieving superficies with acrid-cold decreased the levels of serum TNF-alpha and IL-6 in 5 to 7 days after infection, increased the level of serum IL-1 on the 3rd day after infection, decreased the level of serum IL-1 on the 7th day after infection, significantly increased the levels of serum IL-10 in 1 to 3 days and on the 7th day after infection. The method could be against inflammatory injury. The method of clearing away heat and poison decreased the levels of serum TNF-alpha, IL-6, IL-1 after infection in 3 to 5 days and on the 7th day, and significantly increased IL-10 each time after infection. It exhibited more strong inhibition of inflammatory injury and repair. The method of replenishing Qi significantly decreased the level of serum TNF-alpha and IL-6 in 3 to 7 days after infection, increased the level of serum IL-1 the first 3 days after infection, but decreased the level of serum IL-1 on the 7th day after infection. The method significantly increased the levels of serum IL-10 in 3 to 5 days and on the 7th day. It exhibited inhibition of inflammatory injury. The method of relieving superficies with acrid-cold significantly increased the levels of serum IFN-gamma in 3 days after infection, while the methods of clearing away heat and poison and replenishing Qi significantly increased the levels of serum IFN-gamma in 1 to 3 days and on the 7th day. They exhibited anti-virus and suppression of the immune injury. CONCLUSION: Chinese medicine could correct the imbalance of inflammatory cytokines and be against injury, promote injury restoration, and protect the body.

[The mechanism of signal extension in Haoqin Qingdan decoction immunity activity in Damp-heat syndrome of pneumonia disease infected by influenza virus].

OBJECTIVE: To explore the immunoregulation existing signal transduction mechanism, to evaluate the role of lay its experimental basis By using Haoqin Qingdan decoction for treatments on the mouse models. METHODS: A total of 40 NIH Mice were randomly divided into five groups: control group, virus group (infecting by influenza virus), complex model group (richly fatty and sweet diet + Humid heat environment + infecting by influenza virus), virazole group (mouse of model group was treated by virazole), and Haoqin Qingdan decoction group (mouse of complex model group was treated by decoction of Haoqin Qingdan). When the complex model was established, determination of the mice lung indexes in each group and calculate the inhibition of lung indexes. The level of TLR2 mRNA and NF-κB mRNA expressions of peritoneal macrophages in each group of mice were quantitated by reverse transcription-polymerase chain reaction (RT-PCR). The level of IL-4 and IFN-γ in mouse serum was detected by ELISA to calculate the Th1/Th2 (IFN-γ/IL-4). RESULTS: The lung index of control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group were separately: (0.79 ± 0.11)%, (1.93 ± 0.38)%, (1.41 ± 0.26)%, (1.10 ± 0.26)% and (1.02 ± 0.16)%; The mice of virazole group and Haoqin Qingdan decoction group lung index were decreased (t = 0.322, P < 0.05). TLR2 mRNA expression The results showed that the control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group were: 0.145 ± 0.017, 0.991 ± 0.149, 0.903 ± 0.124, 0.257 ± 0.03 and 0.413 ± 0.031; Compared to the complex model group, Haoqin Qingdan decoction group and virazole group were decreased (t = 0.422, F = 112.834, P < 0.05). Control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group NF-κB mRNA expression were separately: 0.075 ± 0.148, 0.379 ± 0.019, 0.291 ± 0.012, 0.169 ± 0.026 and 0.175 ± 0.033; the expression in virazole group and Haoqin Qingdan decoction group were decreased (t = 0.422, F = 112.834, P < 0.05). The level of IFN-γ in mice serum of control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group were: (7434.06 ± 323.27) pg/ml, (8679.77 ± 198.70) pg/ml, (8068.78 ± 113.8) pg/ml, (7454.66 ± 301.30) pg/ml and (7484.56 ± 229.85) pg/ml respectively; the IFN-γ level in serum of Haoqin Qingdan decoction group and virazole group were decreased (t = 0.201, F = 5.390, P < 0.05). Each group of mice IL-4 contents were (3701.74 ± 256.00) pg/ml, (3569.64 ± 161.35) pg/ml, (3530.88 ± 334.63) pg/ml, (3481.84 ± 282.25) pg/ml and (3618.00 ± 262.16) pg/ml; there were no significant difference between each group (t = 0.414, F = 0.505, P > 0.05). Th1/Th2 type cells in state of equilibrium (means IFN-γ/IL-4) were: 2.02 ± 0.19, 2.38 ± 0.10, 2.36 ± 0.14, 2.22 ± 0.17 and 2.07 ± 0.15; and complex model group Haoqin Qingdan decoction group and virazole group were decreased, and there was no significant difference observed (t = 0.587, F = 3.684, P > 0.05). CONCLUSION: The effect of Haoqin Qingdan decoction on treatment of damp-heat syndrome of pneumonia infected by influenza virus was observed. Through reducing the expressions of TLR2, it decreases the levels of NF-κB mRNA and the proportionality of Th1/Th2 are obviously descend (P < 0.05). Haoqin Qingdan decoction can reduce the lung index and relieve the pathogenic changes.

Antiviral activity of the effective monomers from Folium Isatidis against influenza virus in vivo.

In order to evaluate the anti-influenza virus activity of the effective monomer from Folium Isatidis (FI) in vivo, we established mice model with viral pneumonia and divided them into 3 different dose groups, then observed their lung indexes, pulmonary pathological changes, pulmonary virus hemagglitination titers, living time and death rates. The results showed that the monomer could reduce the pulmonary index from 2.64 to 1.93, 1.63 and 1.40 (P<0.01) and decrease the hemagglitination titer from 1.15 to 0.84, 0.70 and 0.59 (P<0.01). In addition, different groups of FI could significantly lessen the mortality rate from 100% to 30%, 25% and 15%, and prolong the living time from 5.1d to 6.5d, 8.4d and 8.9 d respectively(P<0.01). The high dose (75 mg/kg/d) has the similar effect with 100 mg/kg/d dose of virazole(P>0.05), and more effective than 200 mg/kg/d dose of antiviral liquor (P<0.05).

[Antivirus effects of extract from gardenia].

OBJECTIVE: To observe the effect of the extract from gardenia on influenza viral pneumonia in mice and virus-induced cytopathic effect. METHOD: The mice were infected by influenza virus in nasal, the lung inflammation, mortality rate and life elongation rate were observed respectively. The anti-viral activity of the extract from gardenia was accessed by cytopathic effect (CPE) in vitro and 0% toxicity concentration (TC0), 50% toxicity concentration (TC50), 50% inhibitor concentration (IC50), therapeutic index (TI) were determined by Reed-Muench method. RESULT: The pneumonia induced by influenza virus in mice was inhibited significantly by the extract from gardenia, as the mortality rate decreased and the life elongation rate increased remarkably. Meanwhile the NO content in serum decreased significantly; The cytopathic effect induced by six kinds of viruses was inhibited remarkably. CONCLUSION: The six kinds of viruses were inhibited significantly by the extract from gardenia which inhibitory effect on mice influenza viral pneumonia was related to the NO content decreased.

Antioxidants and viral infections: host immune response and viral pathogenicity.

Malnutrition has long been associated with increased susceptibility to infectious disease. The increase in severity from and susceptibility to infectious disease in malnourished hosts is thought to be the result of an impaired immune response. For example, malnutrition could influence the immune response by inducing a less effective ability to manage the challenge of an infectious disease. Work in our laboratory has demonstrated that not only is the host affected by the nutritional deficiency, but the invading pathogen is as well. Using a deficiency in selenium (Se) as a model system, mice deficient in Se were more susceptible to infection with coxsackievirus, as well as with influenza virus. Se-deficient mice develop myocarditis when infected with a normally benign strain of coxsackievirus. They also develop severe pneumonitis when infected with a mild strain of influenza virus. The immune system was altered in the Se-deficient animals, as was the viral pathogen itself. Sequencing of viral isolates recovered from Se-deficient mice demonstrated mutations in the viral genome of both coxsackievirus and influenza virus. These changes in the viral genome are associated with the increased pathogenesis of the virus. The antioxidant selenoenzyme, glutathione peroxidase-1, was found to be critically important, as glutathione peroxidase knockout mice developed myocarditis, similar to the Se-deficient mice, when infected with the benign strain of myocarditis. This work points to the importance of host nutrition in not only optimizing the host immune response, but also in preventing viral mutations which could increase the viral pathogenicity.

Structure of the hemagglutinin precursor cleavage site, a determinant of influenza pathogenicity and the origin of the labile conformation.

The membrane fusion potential of influenza HA, like many viral membrane-fusion glycoproteins, is generated by proteolytic cleavage of a biosynthetic precursor. The three-dimensional structure of ectodomain of the precursor HA0 has been determined and compared with that of cleaved HA. The cleavage site is a prominent surface loop adjacent to a novel cavity; cleavage results in structural rearrangements in which the nonpolar amino acids near the new amino terminus bury ionizable residues in the cavity that are implicated in the low-pH-induced conformational change. Amino acid insertions at the cleavage site in HAs of virulent avian viruses and those of viruses isolated from the recent severe outbreak of influenza in humans in Hong Kong would extend this surface loop, facilitating intracellular cleavage.

Inhibition of the fusion-inducing conformational change of influenza hemagglutinin by benzoquinones and hydroquinones.

Influenza hemagglutinin (HA) undergoes a conformational change that is required for viral entry. The rearrangement includes exposure of the fusion peptide, a hydrophobic segment buried in the trimer interface of the native protein. Since fusion peptide release triggers the membrane fusion event crucial for viral replication, inhibition of fusion peptide exposure should prevent infection. We reasoned that small molecules that bind to HA and stabilize its nonfusogenic conformation would block viral activity. A computer-assisted method was used to select putative HA ligands. One of the selected compounds, 4A,5,8,8A-tetrahydro-5,8-methano-1,4-naphthoquinone, prevented the conversion of X31 HA to a conformation recognized by alpha-fusion peptide antisera. Several derivatives of this compound, including both benzoquinones and hydroquinones, also showed inhibition. The most effective compounds tested have IC50S between 1 and 20 microM. Representative compounds also inhibited virus-induced syncytia formation, HA-mediated hemolysis, and viral infectivity in vitro. The inhibitors are attractive leads for the development of antiviral drugs and can serve as probes of the mechanism of the conformational change of HA.

Attachment of influenza C virus to human erythrocytes.

Binding experiments with radioactively labelled influenza C virions were carried out to investigate the interaction of the virus with human erythrocytes. The erythrocytes from any of 35 different individuals were found to contain influenza C virus-binding sites though their number was variable among the individuals and was much less than that on mouse, rat and chicken erythrocytes. Attachment of influenza C virus to human erythrocytes was inhibited completely by prior treatment of the virus with anti-HE monoclonal antibody having a strong haemagglutination inhibition activity. Pretreatment of erythrocytes with neuraminidase or the neuraminate-O-acetylesterase of influenza C virus resulted in a marked reduction in the level of virus binding. Thus it appears that human erythrocytes have a low level of O-acetylated sialic acid-containing glycoconjugates that can interact specifically with the HE glycoprotein of influenza C virus. Proteolytic digestion of erythrocytes with ficin, bromelain or V-8 protease inhibited virus binding almost completely, suggesting that the erythrocyte receptor for influenza C virus is a glycoprotein. In contrast to these enzymes, trypsin treatment of erythrocytes reduced virus binding by only about 50%, and alpha-chymotrypsin treatment did not inhibit at all. It was also found that treatment of erythrocytes with monoclonal antibody to the M or N blood group antigen greatly inhibited virus binding to the cells. These results, taken together, suggest that most influenza C virus receptors on human erythrocytes, if not all, reside on glycophorin A which is known to possess the M or N blood group activity.