Research progress on the nucleoside/nucleotide-loaded nanomedicines / 浙江大学学报·医学版

Nucleoside drugs play an essential role in treating major diseases such as tumor and viral infections, and have been widely applied in clinics. However, the effectiveness and application of nucleoside drugs are significantly limited by their intrinsic properties such as low bioavailability, lack of targeting ability, and inability to enter the cells. Nanocarriers can improve the physiological properties of nucleoside drugs by improving drug delivery efficiency and availability, maintaining drug efficacy and system stability, adjusting the binding ability of the carrier and drug molecules, as well as modifying specific molecules to achieve active targeting. Starting from the design strategy of nucleoside drug nanodelivery systems, the design and therapeutic effect of these nanomedicines are described in this review, and the future development directions of nucleoside/nucleotide-loaded nanomedicines are also discussed.

Effect evaluation of medical insurance policy for hepatitis C DAA drugs based on patient survey / 中国药房

OBJECTIVE To provide reference for the prevention and treatment of hepatitis C and the formulation and improvement of medical insurance payment policy for direct-acting antiviral （DAA） drugs. METHODS An questionnaire survey was conducted among the patients who received hepatitis C treatment in a third-grade class-A hospital in Sichuan province from 2019 to 2020 and enjoyed Chengdu medical insurance policy. The patients’ hepatitis C treatment and satisfaction with the medical insurance policy for DAA drugs were compared before and after DAA drugs were included in the medical insurance list. RESULTS A total of 203 patients effectively responded among 644 investigated patients. In terms of treatment plans， although there were significant differences in the treatment plan between patients who saw a doctor in 2019 and 2020 （P＜0.05）， the vast majority of patients were cured within the course of treatment （200 cases， 98.52%）， and there were no obvious adverse reactions （193 cases， 95.07%）. In terms of economic burden， the out-of-pocket costs and economic burden of patients treated with DAA drugs in 2020 were significantly lower than those treated with DAA drugs in 2019 （P＜0.05）； in terms of patient services， 78.82% of patients received expert consultation services from designated medical institutions， but 9.85% of patients still did not receive any patient services provided by the hospital. In terms of satisfaction with outpatient reimbursement policy， the overall satisfaction of patients who saw a doctor in 2020 （95.37%） was significantly higher than those who saw a doctor in 2019 （81.05%）（P＜0.05）. CONCLUSIONS The surveyed patients with hepatitis C obtain good efficacy after DAA drugs treatment， and are satisfied with the medical insurance policy of DAA drugs， but the standardized management of patient services in designated medical institutions is insufficient.

Interpretation of Expert Consensus on Antiviral Therapy of COVID-19 / 中华临床感染病杂志

Novel coronavirus infection(COVID-19)has spread rapidly around the world since its emergence in 2019, with universal susceptibility of the population, causing hundreds of millions of infections and millions of deaths worldwide. Recently, the World Health Organization reconfirmed that COVID-19 is still a public health emergency of international concern. In order to ensure the early detection, identification and intervention of severe COVID-19 cases, reduce the disease severity and mortality, and further standardize the application of antiviral drugs for treatment, the National Center for Infectious Diseases (NCID) has invited experts to develop the Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( Trial version 10) in January 2023. The expert consensus is an important document that systematically reviews, summarizes and analyzes the application of antiviral drugs for COVID-19 from a multidisciplinary perspective for the first time, and can provide guidance and reference for medical institutions at all levels in the selection of antiviral drugs for COVID-19. This article aims to interpret the main points of the expert consensus, including the current epidemiological situation and pathogenic characters of novel coronavirus, clinical characteristics and classification of COVID-19, focusing on the antiviral therapy, guidance for home treatment and post-discharge management of patients with COVID-19.

Research on expression of Toll-like receptors and IFN-α in HCV infected patients with different clinical outcomes / 中国热带医学

@#Abstract: Objective To investigate the changes in expression of Toll-like receptor 3 (TLR3) and interferon-α (IFN-α) in patients with different clinical outcomes of hepatitis C virus (HCV) infection treated with direct-acting antiviral agents (DAAs), and to explore the relationship between the expression of TLR3 and IFN-α with the clinical outcomes of HCV infection. Methods A total of 149 HCV infected patients who received initial treatment were selected from Hainan General Hospital between September 2020 and August 2022. The patients were divided into two groups: chronic hepatitis C (CHC) group (n=129) and liver cirrhosis (LC) group (n=20). Additionally, 28 volunteers were selected as the control group during the same period. All patients with HCV infection were first treated with Sofosbuvir/Vipatavir tablets for 12 weeks. Blood samples were collected at 0, 4, 12, 24 and 48 weeks after treatment. Liver function indicators were detected by enzyme-linked immunosorbent assay (ELISA), while TLR3 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction (qRCR), IFN-α was detected by Luminex multiplex cytokine assays. Measurement data subject to normal distribution were represented by x±s, and t test was used between groups. Compare differences between groups. Results TLR3 mRNA in CHC group was higher than that in LC group and control group at baseline (P<0.05). After 4 weeks of DAAs treatment, TLR3 mRNA in CHC and LC groups was significantly up-regulated (P<0.05). TLR3 mRNA in the CHC group was gradually down-regulated to the level of the control group at 12, 24, and 48 weeks. In addition, IFN-α expression gradually increased with prolonged treatment, while it decreased in the LC group. The liver inflammation indicators in both the CHC and LC groups partially recovered after treatment with DAAs. Conclusions TLR3 is involved in viral clearance and chronic inflammatory response. The expression difference of TLR3 in patients with different clinical outcomes of HCV infection after DAAs treatment may be related to the severity of the disease.

Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir (VV116) / 医学前沿

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.

Hepatocellular carcinoma post direct anti hepatitis C viral agents; clinical features

Background: Direct Anti Hepatitis C Viral Agents (DAAs) were introduced for Hepatitis C Virus (HCV) infection management, which resulted in high sustained virological response (SVR) in many countries and a low failure rate. However, hepatocellular carcinoma (HCC) post DAAs therapy is controversial; few studies related aggressive pattern HCC to DAAs. Therefore, we aimed to study the hepatocellular carcinoma relation to direct anti-hepatitis C viral drugs. Patients and Methods: This observational cross-sectional study included 67 adults Egyptian HCC patients associated with HCV diagnosed at the Zagazig University Hospitals, who were divided into two groups according to DAAs treatment. Results: HCC is more common in male patients (77.6%) of all studied cases, and those are treated by DAAs (62.7%). The median age of HCC post-DAA was 63(48-83), while 58 (45-75) in HCC patients without DAA, with no significant difference p= 0.053. HCC presented in the non-DAAs treated group, mainly decompensating by hematemesis (HM) (32%). While in the post-DAAs group, HCC was significantly diagnosed primarily with abdominal pain at 31%. There is no significant difference as regards the liver status with frequent liver cirrhosis in both groups, 14(56%) and 32(76.2%). Conclusion: DAAs therapy of HCV added no specific pattern association for hepatocellular carcinoma.

Medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

Naturally occurring resistance-associated variants to NS3/4A protease and NS5A inhibitors in patients with HIV/HCV co-infection or HCV infection alone / 临床肝胆病杂志

Objective To investigate the difference in naturally occurring resistance-associated variants (RAVs) between the patients with HIV/HCV co-infection and those with HCV infection alone by detecting the drug resistance loci associated with HCV NS3/4A protease and NS5A inhibitors. Methods A total of 246 patients with HIV/HCV co-infection or HCV infection alone who were hospitalized or attended the outpatient service in Guangzhou Eighth People's Hospital, Guangzhou Medical University, from January 2016 to January 2020 were enrolled in this study. Serum samples were collected and next-generation sequencing (Illumina platform, PE250) was used for sequencing. The two groups of patients were compared in terms of RAVs associated with NS3/4A protease and NS5A inhibitors approved in China, and the drugs for analysis included asunaprevir/daclatasvir (ASV/DCV) and elbasvir/grazoprevir (EBR/GZR) for HCV genotype 1b and glecaprevir/pibrentasvir (GLE/PIB) for pan-genotypes. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Among the 246 serum samples included in this study, 239 samples (97.2%) were successfully amplified by PCR and sequenced, with 102 samples from the patients with HIV/HCV co-infection and 137 from the patients with HCV infection alone. The analysis of RAVs associated with ASV/DCV and EBR/GZR showed that Y56F, Q80K/L, and S122N/R/T associated with ASV and GZR and L31M and Y93H associated with DCV and EBR were observed in patients with HIV/HCV (genotype 1b) co-infection or HCV (genotype 1b) infection alone; 2 patients with HIV/HCV co-infection had the RAVs of Y56F+Y93H associated with EBR/GZR, and 2 with HCV infection alone had the RAVs of Q80L+L31M and Y56F+Y93H, respectively, associated with EBR/GZR, with no significant difference in RAVs between the two groups (both P > 0.05). The analysis of RAVs associated with GLE/PIB for pan-genotypes showed that 3 patients with PIB-associated Y93H RAV were observed among the patients with HCV genotype 3a infection, among whom 2 had HIV/HCV co-infection and 1 had HCV infection alone ( P =0.590), and in addition, no RAVs associated with GLE/PIB were observed. Conclusion There is no significant difference in naturally occurring RAVs associated with HCV NS3/4A protease and NS5A inhibitors between the patients with HIV/HCV co-infection and those with HCV infection alone.

Efficacy and safety of ledipasvir/sofosbuvir versus elbasvir/grazoprevir in treatment of genotype 1b chronic hepatitis C / 中华临床感染病杂志

Objective:To compare the clinical efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) in treatment of patients with chronic hepatitis C (CHC).Methods:The clinical data of 143 patients with genotype 1b CHC treated in Huzhou Central Hospital from January 2020 to December 2021 were retrospectively analyzed, including 74 cases treated with LDV/SOF and 69 cases treated with EBR/GZR. The virological response after 4 and 12 weeks of treatment and 12wk after drug withdrawal was determined; and the serological and liver inflammation indexes before and after treatment in two groups were compared. SPSS 25.0 software was used for statistical analysis of the data.Results:The virological response rates of the LDV/SOF group and EBR/GZR group were 97.30% and 98.55%, 98.65% and 100.00%, 97.30% and 98.55% after 4 and 12 weeks of treatment and 12 weeks after the end of treatment, respectively (all P > 0.05). At the end of treatment, the liver inflammation indexes ALT, AST and GGT in the two groups were significantly lower than the baseline levels ( Z=-7.470 and -6.974, -9.757 and -6.832, -3.578 and -4.054, P<0.01). Adverse reactions in both groups were mild, and no serious adverse events occurred. Conclusion:Both LDV/SOF and EBR/GZR have good clinical efficacy in the treatment of genotype 1b CHC patients. And the patients are well tolerated.

Latest progress in the development of anti-2019-nCoV therapeutic drugs / 中华临床感染病杂志

In recent years, great progress has been made in small molecule therapeutic drugs and monoclonal neutralizing antibody preparations against 2019-nCoV. At least 5 oral drugs (Monupavir, AT-527, Proclutamide, Paxlovid and S-217622) and 2 monoclonal antibodies (Ambavirumab/Romisevirumab combination and Sotrovimab) have completed phase Ⅲ clinical trials exhibiting excellent antiviral effects. This article reviews the research progress of these 7 drugs to provide reference for clinical application.

Clinical observation of Rougan Huaxian granule combined with nucleoside antiviral drugs in treatment of patients with decompensated cirrhosis of hepatitis B / 中国综合临床

Objective:To explore the effects of Rougan Huaxian Granules combined with nucleoside antiviral drugs on liver and kidney function, portal hemodynamics, vascular activity, antiviral indexes and aspartate transaminase-platelet ratio index in patients with hepatitis B decompensated cirrhosis.Methods:A case-control study was conducted on 150 patients with hepatitis B decompensated cirrhosis who were hospitalized in Tangshan Infectious Disease Institute and Affiliated Hospital of North China University of Science and Technology from June 2017 to December 2019 were enrolled. The patients were divided into control group and observation group by computer random random number method, with 75 cases in each group. The control group was given routine liver protection and antiviral treatment; the observation group was given Rougan Huaxian granules on the basis of the control group treatment. Observe the changes of liver and kidney function, portal vein system hemodynamics, vascular activity, antiviral index and aspartate transaminase-platelet ratio index in the two groups. Independent sample T test was used to compare the measurement data between the two groups, paired T test was used for comparison between the same groups before and after treatment, and χ2 test was used for counting data. Results:There were no significant differences in gender, age, course of cirrhosis, Child grade of liver function and baseline data of indexes before treatment between 2 groups (ALL P>0.05). After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen, creatinine,diameter of portal vein (Dpv), diameter of splenic vein (Dsv), endothelin-1, nitric oxide, glucagon (GLA), APRI,were all lower than before treatment. Comparison between groups, observation group ALT (51.60±15.97) U/L, AST (62.65±26.28) U/L, urea nitrogen (10.25±1.65) mmol/L, creatinine (78.54±14.09) μmol/L, Dpv (10.20±1.10) mm, Dsv (8.08±0.68) mm, endothelin-1 (31.93±6.35) ng/L, nitric oxide (41.38±8.06) μg/L, GLA (69.54±12.14) mg/L, APRI (3.14±1.35), were significantly lower than those of control group ((97.49±30.87) U/L, (96.03±25.63) U/L, (17.49±2.55) mmol/L, (116.43±22.77) μmol/L, (13.42±1.26) mm, (10.44±0.83) mm, (44.34+11.88) ng/L, (63.47±15.50) μg/L, (107.11+25.29) mg/L, (5.91±1.93)), the differences were statistically significant ( t values were respectively 11.43, 7.87, 20.64, 12.26, 16.62, 18.99, 7.98, 10.96, 11.60, 10.23, all P<0.05). After treatment, albumin, portal vein velocity (Vpv), and velocity of splenic vein blood flow (Vsv) were all higher in the two groups than before treatment. However, there was no significant difference in Vsv of the control group before and after treatment ( t=0.51, P=0.613). Comparison between groups, albumin (39.42±7.35) g/L, Vpv ((25.72±4.06) cm/s), Vsv ((24.22±6.15) cm/s) in the observation group were significantly higher than those in the control group (34.66±7.95) g/L, (19.38±3.46) cm/s, (19.54±5.88) cm/s ( t values were 3.81, 10.28, 4.76, all P<0.05). After treatment, the total effective rate (96.00%(72/75) vs. 86.67%(65/75), χ2=4.13, P=0.042), HBV DNA negative conversion rate (76.00%(57/75) vs. 58.67%(44/75), χ2=5.12, P=0.024), HBeAg negative conversion rate (50.67%(38/75) vs. 30.67%(23/75), χ2=6.22, P=0.013) and serum HBeAg/HBeAb conversion (28.00%(21/75) vs. 13.33%(10/75), χ2=4.92, P=0.027) in observation group were higher than those in control group, and the differences were statistically significant ( P<0.05). HBsAg negative rate (8.00%(6/75) vs. 5.33%(4/75), χ2=0.43, P=0.513) was higher than that of control group, but the difference was not statistically significant ( P>0.05). Conclusion:Rougan Huaxian Granules combined with nucleoside antiviral drugs has significant effect on patients with decompensated liver cirrhosis of hepatitis B, improve liver and kidney function, liver fibrosis and hemodynamics of the portal vein system, increase vascular activity function, and reduce hepatitis B virus (HBV) DNA load, HBV replication, aspartate transaminase-platelet ratio index, APRI, Toll-like receptor (TLR-4) and transforming growth factor β1 (TGF-β1) levels and improves the body′s immune status.

Falla hepática aguda sobre crónica por exacerbación de hepatitis B asociada a suspensión de la terapia antiviral: reporte de caso / Acute-on-chronic liver failure caused by hepatitis B flare associated with stopping antiviral therapy: case report

El principal objetivo del tratamiento de la infección por virus de la hepatitis B es prevenir la replicación viral, con el fin de evitar las posibles complicaciones asociadas a la infección, como son las exacerbaciones o flares, las cuales pueden llegar a ser tan severas que causan una falla hepática aguda sobre crónica (ACLF). La ACLF se asocia con falla multiorgánica y una alta mortalidad, y puede ser desencadenada por la reactivación de hepatitis virales, infecciones bacterianas y consumo de alcohol, entre otros factores. Aunque la fisiopatología de la ACLF no es clara aún, parece haber una respuesta inflamatoria excesiva asociada con esta condición. El uso de análogos de nucleótidos/nucleósidos en el tratamiento de la hepatitis B crónica reduce el riesgo de morbilidad y mortalidad asociadas a la progresión de la enfermedad hepática, pero la terapia a largo plazo tiene sus limitaciones por el alto costo y por el riesgo asociado al uso indefinido. Debido a esto, en los últimos años se ha venido considerando la interrupción de la terapia en algunos pacientes por parte de las diferentes asociaciones; no obstante, aún no hay consenso en cuanto al mejor momento para hacerlo. Se describe el caso clínico de un paciente con cirrosis compensada por hepatitis B, con HBsAg positivo y HBeAg inicialmente negativo, a quien se le suspendió el tratamiento con entecavir por decisión médica, presentando una ACLF por exacerbación de la hepatitis B, con posterior deterioro y muerte del paciente. Se debe realizar una caracterización adecuada de cada paciente antes de suspender el tratamiento.

The main objective of treating hepatitis B virus infection is to prevent viral replication in order to avoid possible complications, including flares which can become so severe that can cause an acute over chronic liver failure (ACLF). ACLF is associated with multiple organ failure and high mortality, and can be triggered by reactivation of viral hepatitis, bacterial infections and alcohol consumption, among other factors. Although the pathophysiology of ACLF is not yet clear, there appears to be an excessive inflammatory response associated with this condition. The use of nucleotide/nucleoside analogs in chronic hepatitis B reduces the risk of morbidity and mortality related to the progression of the disease, but long-term treatment has its limitations due to the high cost and the risk of indefinite therapy. Due to this, in recent years the stopping of therapy in some patients has been considered by the different associations; however, there is currently no consensus as to the best time to do it. We present a clinical report of a patient with compensated hepatitis B cirrhosis, with positive HBsAg and initially negative HBeAg, who stopped treatment with entecavir by medical instruction, developing ACLF due to exacerbation of hepatitis B, with subsequent deterioration of the patient condition and ultimately death. An adequate characterization of each patient must be carried out before stopping treatment.

Progress in the treatment of chronic hepatitis C virus genotype 3 infection / 中华临床感染病杂志

Hepatitis C virus genotype 3 (HCV G3) infection is the second most prevalent hepatitis C genotype globally, with higher rates of disease progression and mortality compared with other genotypes. After the advent of direct-acting antiviral drugs (DAAs), the efficacy of antiviral therapy for hepatitis C patients has been greatly improved, but the therapy for G3 type is less effective than that for other genotypes, so it is considered to be one of the most difficult subtypes to treat. This article reviews the available treatment options for HCV G3 patients and their sustained virological response rates to provide clinical reference.

Potential Therapeutic Avenues For Covid-19 Therapy

Covid-19, an infectious disease caused by coronavirus spreads by salivary droplets or nasal discharge from an infected person during sneezing or coughing. This infectious disease is caused by a novel coronavirus, SARS CoV-2 shares the same structure with that of the virus that causes severe acute respiratory syndrome (SARS). Most of the people who are infected with Covid-19 will experience respiratory illness and can be treated with antiviral drugs and or a combination of antiviral drugs and supportive therapies. Many medical investigational approaches are being investigated to design possible treatment strategies and possible avenues for Covid-19 therapy. Potential strategies for the treatment of Covid-19 include antiviral medication, the combination of interferons and antiviral drugs, interleukin inhibitors. Recent studies show that the use of plasma from survivors can help patients in recovering from the disease. This approach of using plasma is termed as convalescent plasma therapy. Another newer technology that includes the construction of a recombinant vaccine is gaining importance for further investigation. The other major approaches include the therapeutic use of serine protease inhibitors, chloroquine, hydroxychloroquine, ammonium chloride in definite doses. New study approaches include investigation on the production of monoclonal antibodies has gained a way for further clinical research. An effective supportive therapy includes extracorporeal membrane oxygenation could be considered as rescued therapy for the patients having respiratory distress. After sufficient clinical data is obtained and by taking all these approaches into consideration, the treatment protocol can be designed to treat Covid-19 successfully.

Preprocesamiento de los fármacos antivirales candidatos contra COVID-19 en modelos de SARS cov2. Objetivos / Preprocessing of the candidate antiviral drugs against COVID-19 in models of SARS cov2 targets

Although many viral infections are self-limiting, other are real health challenges like COVID-19 since many viruses possess just few drug gable targets to be treated with small drug molecules. Corona virus genome encodes for up to 17 main proteins. Orf1ab encodes for polyprotein. COVID-19 structural proteins are the spike S, membrane M, envelope E and the nucleocapsid N protein while other are non-structural proteins designated as NSP1-13 for non-structural proteins. Among NSP the most important corona virus targets for developing antiviral drugs are the papain-like protease, PDB ID: 6m03 and RNA polymerase NSP12, PDB ID: 6nur. NCBI, NIH Genbank, Uniprot, PDB, DrugBank, ChemSpider databases and bioinformatics editor softwares like ICM Mol soft pro and Swiss Dock were used in addition to the in vitro lab model of viral protease were integrated to retrieve and analyze corona virus targets and to select the candidate ligands in an attempt to evaluate the inhibitory efficacy of different experimental and approved drugs which were further optimized and searched for the highly similar approved drug. This step aims to adopt drug repurposing to speed the development of antiviral drugs and recommend rational in vivo and clinical studies. After COVID-19 targets had been analyzed the drugs that shared > 70% similarity to the binding sites of those targets were reversin, pentagastrin, remdesivir, norfloxacin and nitazoxanide against COVID-19 papain-like protease whereas benzyl glutathione, lopinavir and hydroxymethylglutathione against RNA polymerase. The anti-resistance reversin showed the highest inhibitory efficacy against COVID-19 papain-like protease as indicated by the ligand-protease binding energy with Mol soft pro analysis. The calculated inhibitory binding was -137.30 kJ/mol z > 1.9 as compared with the tetrazapentadecanoate -129.57 kJ/mol z = 4.0, whereas remdesivir, pentagastrin, nitazoxanide and norfloxacin had a moderate antiprotease activity (>- 100 kJ/mol). Norfloxacin shoresults showed a slight consistency between in vitro and in silico models. Although benzyl glutathione is an experimental compound, however it had the highest RNA polymerase inhibiting efficacy with -129 kJ/mol binding energy which is even higher than lopinavir and Favinavir. From the overall results, reversin, oligopeptides, quinolones and antiviral drugs may widen the treatment options for COVID-19 if further evaluated in clinical studies

Pharmacovigilance study on drug-induced cardiac injury during treatment of COVID-19 / 中国中药杂志

Because coronavirus disease 2019(COVID-19) is highly contagious and serious, it has posed a major threat to public health worldwide. The curative effects of integrated traditional Chinese medicine and Western medicine in the treatment of COVID-19 have been widely recognized and confirmed. However, medical workers shall pay attention to drug-induced heart injury in clinical application. Based on the guideline from the Diagnosis and Treatment Plans for COVID-19(trial seventh edition), taking the recommended drugs as examples, by Western medicine, traditional Chinese medicine, Chinese herbal injection and integrated traditional Chinese and Western medicine, the study analyzed the basic characteristics of recommended drugs for cardiac injury by means of literature review and bioinformatics methods, and summarized cardiac adverse reactions, toxicity mechanisms, combined pharmacotherapy, special population and drug monitoring, focusing on the clinical manifestations, toxic components, targets and regulatory mechanisms of drug-induced cardiac injury. The findings suggested being vigilant to drug-induced cardiac injury during the treatment of COVID-19, playing the advantages of clinical pharmacists and clinical Chinese pharmacists, improving the knowledge reserve of pharmacovigilance, strengthening the prescription review, medication notification and medication monitoring, promoting rational drug use and paying attention to special populations and high-risk groups. The study aims to provide suggestions and reference for pharmacovigilance and pharmaceutical care for front-line doctors and pharmacists against COVID-19, in order to avoid the occurrence of drug-induced heart injury for patients with COVID-19.

Andrographolide as a potent and promising antiviral agent / 中国天然药物

Andrographolide is a labdane diterpenoid extracted and purified from the aerial parts of plants belonging to genus Andrographis (Acanthaceae). The research has shown the plant based compound is low cytotoxic, having antimicrobial, anti-cancer, antiviral and anti-parasitic effects. Andrographolide both prevent spread as well as transmission of virus to neighboring cells by interfering with different cell signaling pathways. In addition to its medicinal value, plant has been found having nutritional value. Therefore being cost effective, easy availability and having nutritional value as a natural supplement, can be used to improve the quality of life in countries having low standard of living. Due to the limited number of effective vaccines, the plant-based antiviral drugs have provided considerable hope for fighting against the viral infections. The plant-derived compound when produced in large quantities is cost effective with low cytotoxic effects. However, much deep insight research at the molecular level is needed to develop the molecules against the viral infection. This paper aims to highlight the antiviral role of Andrographolide that can made significant contributions toward the improvement of human health and will also summarize the current status and future strategies concerning the therapeutic applications of Andrographolide to combat different viral disease in humans.

Antiviral therapy for coronavirus disease 2019 / 中南大学学报(医学版)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the outbreak of coronavirus disease 2019 in Wuhan City, China. The SARS-CoV-2 is genetically similar to the coronavirus derived from bat. The SARS-CoV-2, the SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV) all belong to beta coronavirus. Since the outbreak of the coronavirus disease 2019, effective antiviral drugs have become a hot issue in the world. Very little about SARS-CoV-2 is known and there is no precedent for treatment. The National Health Commission has repeatedly revised the diagnosis and treatment guide for the coronavirus disease 2019. The latest guide is "New Coronary Virus-Infected Pneumonia Diagnosis and Treatment Plan (Seventh Trial Version)"(short for Seventh Version of Diagnosis and Treatment Plan). But the use of antiviral drugs is still on trial and no rigorous clinical trials data is available. Hot anti-SARS-CoV-2 drugs include interferon α, ribavirin, lopinavir/ritonavir, chloroquine phosphate, abidol, as well as hydroxychloroquine sulfate and remdesivir. But the later 2 drugs aren't mentioned in the Seventh Version of Diagnosis and Treatment Plan.

Analysis of the mechanism for potential anti-novel coronavirus 2019-nCoV drugs based on diagnosis and treatment guidelines / 国际药学研究杂志

The novel coronavirus pneumonia is an acute respiratory infectious disease caused by novel coronavirus(2019- nCoV). The 2019- nCoV genome sequence and the clinical symptoms caused by 2019- nCoV are different from those of the previous large outbreak of SARS virus, and no specific antiviral drugs are available nowadays. In order to treat pneumonia cases of 2019-nCoV infection, the National Health Commission has released several versions of The Pneumonia Diagnosis and Treatment guidelines for Novel Coronavirus Infection. Based on domestic and foreign literature, this paper briefly describes the clinical efficacy and mechanism of the chemical drugs and traditional Chinese medicines recommended for the treatment of 2019-nCoV infections in the Treatment guidelines, so as to provide a necessary theoretical basis for the selection of anti-2019-nCoV drugs.