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COVID-19 is a severe acute respiratory syndrome caused by a novel coronavirus, SARS-CoV- 2.COVID-19 is now a pandemic, and is not yet fully under control.As the surface spike protein (S) mediates the recognition between the virus and cell membrane and the process of cell entry, it plays an important role in the course of disease transmission.The study on the S protein not only elucidates the structure and function of virus-related proteins and explains their cellular entry mechanism, but also provides valuable information for the prevention, diagnosis and treatment of COVII)-19.Concentrated on the S protein of SARS-CoV-2, this review covers four aspects: (1 ) The structure of the S protein and its binding with angiotensin converting enzyme II (ACE2) , the specific receptor of SARS-CoV-2, is introduced in detail.Compared with SARS-CoV, the receptor binding domain (RBD) of the SARS-CoV- 2 S protein has a higher affinity with ACE2, while the affinity of the entire S protein is on the contrary.(2) Currently, the cell entry mechanism of SARS-CoV-2 meditated by the S protein is proposed to include endosomal and non-endosomal pathways.With the recognition and binding between the S protein and ACE2 or after cell entry, transmembrane protease serine 2(TMPRSS2) , lysosomal cathepsin or the furin enzyme can cleave S protein at S1/S2 cleavage site, facilitating the fusion between the virus and target membrane.(3) For the progress in SARS-CoV-2 S protein antibodies, a collection of significant antibodies are introduced and compared in the fields of the target, source and type.(4) Mechanisms of therapeutic treatments for SARS-CoV-2 varied.Though the antibody and medicine treatments related to the SARS-CoV-2 S protein are of high specificity and great efficacy, the mechanism, safety, applicability and stability of some agents are still unclear and need further assessment.Therefore, to curb the pandemic, researchers in all fields need more cooperation in the development of SARS-CoV-2 antibodies and medicines to face the great challenge.Copyright © Palaeogeography (Chinese Edition).All right reserved.
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Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg.kg-1), and positive control sildenafil group (100 mg.kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% +/- 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF- kappaB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF- kappaB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-kappaB and signal transducer and activator of transcription 3 (STAT3) by DYY.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.
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Objective To explore the potential common mechanism and active ingredients of Reduning Injection against SARS, MERS and COVID-19 through network pharmacology and molecular docking technology. Methods The TCMSP database was used to retrieve the chemical components and targets of Artemisiae Annuae Herba, Lonicerae Japonicae Flos and Gardeniae Fructus in Reduning Injection. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.8.2 was used to build a medicinal material-compound-target (gene) network. Three coronavirus-related targets were collected in the Gene Cards database with the key words of "SARS""MERS" and "COVID-19", and common target of three coronavirus infection diseases were screened out through Venny 2.1.0 database. The common targets of SARS, MERS and COVID-19 were intersected with the targets of Reduning Injection, and the common targets were selected as research targets. Protein-protein interaction (PPI) network map were constructed by Cytoscape3.8.2 software after importing the common targets into the STRING database to obtain data. R language was used to carry out GO biological function enrichment analysis and KEGG signaling pathway enrichment analysis, histograms and bubble charts were drew, and component-target-pathway network diagrams was constructed. The key compounds in the component-target-pathway network were selected for molecular docking with important target proteins, novel coronavirus (SARS-CoV-2) 3CL hydrolase, and angiotensin-converting enzyme II (ACE2). Results 31 active compounds and 207 corresponding targets were obtained from Reduning Injection. 2 453 SARS-related targets, 805 MERS-related targets, 2 571 COVID-19-related targets, and 786 targets for the three diseases. 11 common targets with Reduning Injection: HSPA5, CRP, MAPK1, HMOX1, TGFB1, HSP90AA1, TP53, DPP4, CXCL10, PLAT, PRKACA. GO function enrichment analysis revealed 995 biological processes (BP), 71 molecular functions (MF), and 31 cellular components (CC). KEGG pathway enrichment analysis screened 99 signal pathways (P < 0.05), mainly related to prostate cancer, fluid shear stress and atherosclerosis, hepatocellular carcinoma, proteoglycans in cancer, lipid and atherosclerosis, human T-cell leukemia virus 1 infection, MAPK signaling pathway, etc. The molecular docking results showed that the three core active flavonoids of quercetin, luteolin, and kaempferol in Reduning Injection had good affinity with key targets MAPK1, PRKACA, and HSP90AA1, and the combination of the three active compounds with SARS-CoV-2 3CL hydrolase and ACE2 was less than the recommended chemical drugs. Conclusion Reduning Injection has potential common effects on the three diseases of SARS, MERS and COVID-19. This effect may be related to those active compounds such as quercetin, luteolin, and kaempferol acting on targets such as MAPK1, PRKACA, HSP90AA1 to regulate multiple signal pathways and exert anti-virus, suppression of inflammatory storm, and regulation of immune function.Copyright © 2022 Drug Evaluation Research. All rights reserved.
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Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.
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Background. The rapidly developing resistance of viruses to synthetic antiviral drugs indicates the need to use substances with multitarget action (to avoid polypharmacy and to improve the safety of treatment). Objective(s): systematic analysis of the scientific literature on the pharmacology of bioflavonoids with an emphasis on their antiviral action. Material and methods. More than 150,000 references of primary sources were found in the PubMed/MEDLINE database of biomedical publications, including 3282 references on the antiviral effects of bioflavonoids. A systematic computerized analysis of this array of publications was carried out in order to identify the main directions in the pharmacology of bioflavonoids with an emphasis on their antiviral, antibacterial and immunomodulatory effects. The literature analysis was carried out using modern methods of topological and metric analysis of big data. Results. The molecular mechanisms of action of baicalin, hesperidin, rutin, quercetin, leukodelphinidin bioflavonoids and epigallocatechin-3gallate, curcumin polyphenols, their anti-inflammatory, antioxidant, antiviral, bactericidal, angioprotective, regenerative effects, and their prospects in therapy, prevention and rehabilitation of patients with COVID-19 and other respiratory viral infections were described in detail. Conclusion. Bioflavonoids and synergistic polyphenols exhibit not only multitarget antiviral effects by inhibiting the main protease, spike proteins, and other target proteins, but also pronounced anti-inflammatory, hepatoprotective, and immunomodulatory effects.Copyright © 2023 Modern Medical Technology. All rights reserved.
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At present, coronavirus disease-19 (COVID-19) caused by novel coronavirus (SARS-CoV-2) has been spreading around the world, but no specific therapeutic drug or vaccine has been developed for the virus. By collecting the latest literature and searching related database websites, the biological characteristics and main targets of SARS-CoV-2, the clinical therapeu tic drugs and the latest drug research were reviewed to provide information for clinical treatment and provide reference for the research and development of new drugs against SARS-CoV-2.Copyright © 2020 Publication Centre of Anhui Medical University. All rights reserved.
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The use of convalescent plasma (CP) transfusions for patients with coronavirus disease 2019 (COVID-19) has gained great interest during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. This review aims at summarizing the literature on the potential mechanisms of action of COVID-19 CP (CCP) and the rationale for use. A narrative review of the literature was conducted using PubMed, Google Scholar, and the Cochrane Database through October 2020. The rationale of CCP deployment was based on historical use in other outbreaks and pandemics and the emergent need at the time of lack of proven therapies and vaccines. There are many proposed mechanisms of action including direct neutralization and suppression of viremia, antibody-dependent cellular cytotoxicity, modification of the inflammatory response, restoration of the coagulation factors, immunomodulation of the hypercoagulable state and the potential role of ABO naturally occurring iso-agglutinins. Many donor, product, and patient factors can impact the response to CCP, such as antibody titer in the CCP product, CCP dose, frequency of administration, the severity of underlying illness, and the timing of administration from time of disease onset. Based on current evidence, CCP appears to be safe. However, it remains unknown whether it impacts the improvement of clinical symptoms, time to death, and all-cause mortality. In conclusion, the use of CCP offers quick access as an empirical therapy when specific therapies are not available or under development. Ongoing clinical trials are expected to add to the breadth of knowledge on the safety and efficacy of CCP use in patients with COVID-19.Copyright © 2021 AME Publishing Company.
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During the treatment of critically ill COVID-19 patients it has been revealed that the neutralizing monoclonal antibodies against 2019-nCoV have the advantages of high specificity, high purity, and can be prepared in a large scale, which are expected to be a effective preparation for clinical use. This article introduces the way of 2019-nCoV invasion into the host cells, the major variants of novel coronavirus, and the mechanism of action of anti-2019-nCoV monoclonal antibodies, as well as the progress of research and development of their preparation in major pharmaceutical companies, to provide reference for scientific research and clinical application.Copyright © Chinese Journal of Clinical Infectious Diseases.All rights reserved.
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Objective: The purpose of this scoping review is to show the evidence available in the literature and provide an overview of the antimicrobial-containing mouthwashes for reducing viral load in order to group the most up-to-date information and make it more accessible to dentists. Design(s): A structured electronic search in PubMed (Medline), LILACS, EMBASE and EBSCO without temporal restriction was performed. The studies were selected based on their title, and full reading following a pre-established order based on the inclusion and exclusion criteria. The included studies were those that analyzed the effect of viral load reduction by mouthwashes, primary studies, no reviews and in Spanish, English or Portuguese. Result(s): The search resulted in 1881 articles, at the end of the exclusion of duplicates and selection, 71 articles were included in this scoping review. The substances most commonly found were chlorhexidine (CHX), povidone-iodine (PVP-I), essential oils (EO), cetylpyridinium chloride (CPC), hydrogen peroxide (H2O2) and other substances (OTHERS). Conclusion(s): Of all the mouthwashes analyzed, the Essential oils, Cetylpyridinium Chloride and Povidone-iodine, showed antiviral potential against common viruses present in the oral cavity, with no significant side effects in short-term use, and are viable options for use as a pre-procedure in clinical routine against SARS-CoV-2 and other types of viruses. The other solutions need further studies to determine their effect and confirm their clinical use.Copyright © 2023
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Silymarin, is a phytoactive constituent isolated from the fruits and seeds of Silybum maria-num L Gaetn.), also called milk thistle belonging to the family of Asteracease. The phytoactive has been used to treat several physiological disorders. The objective of this manuscript was to review the therapeutic prospective of silymarin due to its ability to treat several physiological disorders. The da-tabases such as Pubmed, Elsevier, and Google Scholar were reviewed for the investigations or reviews published related to the title. The discussion is focused on the immunomodulatory, chemopreventive, and anti-inflammatory mechanisms of silymarin in various metabolic and dermatological disorders. In addition, the review discusses the different therapeutic potentials of silymarin such as the management of the liver disorder, skin carcinogenesis, cardiovascular disorders, diabetes mellitus, neurodegenera-tive disorders, and several dermatological disorders such as melasma, anti-aging, acne, rosacea, atopic dermatitis, and psoriasis. Silymarin is safe even with a dose higher than the therapeutic dose. Si-lymarin had good potential for the safe and effective treatment of numerous metabolic and dermatological disorders. © 2023 Bentham Science Publishers.
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In late 2019 until 2021, the novel coronavirus disease (COVID-19) has become pandemic. This disease is related to severe inflammatory symptoms of the respiratory epithelial cells and the dysfunction of several organs. One of the suggested drugs to reduce the inflammation caused by COVID-19 is hydroxychloroquine. Studies have shown this drug blocks the inflammatory pathway of nuclear factor-kappaB by blocking P21 activated kinase 1. Also, nanoparticle vaccines Poly Lactide-Glycolide) Acid (PLGA) containing hydroxychloroquine are effective in cancer by stimulating CD8T + cells responses. This study assumed that hydroxychloroquine was effective in inhibiting COVID-19 with these mechanisms.Copyright © 2021 Health Biotechnology And Biopharma. All Rights Reserved.
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Interferons (IFNs) were first discovered over 60 years ago in a classic experiment by Isaacs and Lindenman showing that type I IFNs have antiviral activity. IFNs are widely used in the treatment of multiple sclerosis, viral hepatitis B and C, and some forms of cancer. Preliminary clinical data support the efficacy of type I IFN against potential pandemic viruses such as Ebola and SARS. Nevertheless, more effective and specific drugs have found their place in the treatment of such diseases. As the COVID-19 (SARS-CoV-2) pandemic is evolving, type I IFN is being re-discussed as one of the main pathogenic drugs, and initial clinical trials have shown promising results in reducing the severity and duration of COVID-19. Although SARS-CoV-2 inhibits the production of IFN-beta and prevents a full innate immune response to this virus, it is sensitive to the antiviral activity of externally administered type I IFN. The review presents current data on the classification and mechanisms of action of IFN. Possible options for the optimal use of IFN in the fight against COVID-19 are discussed.Copyright © 2022 Ima-Press Publishing House. All rights reserved.
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Garlic (Allium sativum) has been known for its potent medicinal activities and its interesting culinary role since ancient times. With over 200 phytochemicals and flavoring compounds elucidated and many others yet to, garlic promises to improve human health and vitality. Just like other phytochemical classes, essential oils for garlic have been reported to show interesting medical activities delving across diverse antimicrobial, cardio-protective, anti-cancer, anti-Alzheimer, anti-diabetic, and immunomodulatory activities. Garlic essential oils contain mainly volatile and non-volatile allyl-sulphur-based compounds, which are a product of the stream decomposition of Allicin (a major component of garlic extract). Although a lot of work has been done on Allicin, there is little substantive work on the bio-availability and toxicities of its essential oil. This study, however, reviewed the methods that in recent times have been used to extract essential oils from garlic, recent studies on composition and therapeutic activities of Garlic essential oils, and a predictive overview of their bioavailability and toxicity. Finally, recommendations for future studies and other interesting prospects of garlic were also highlighted.Copyright © 2022
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Cardiovascular disease (CVD) is the leading cause of death in most developed countries, including the United States, with a significant economic impact. Lifestyle changes and the administration of antiplatelet medication, like aspirin, may significantly contribute to the secondary prevention of CVD in adults. For years, aspirin has been utilized for both secondary and primary cardiovascular disease prevention. Aspirin has been extensively used because of the belief that it may have a positive impact on primary prevention, despite the debate surrounding its usage. This study briefly examines usage patterns and discusses the potential variables and factors that can decrease the ability of aspirin to prevent cardiovascular disease. The present study also explore the key studies of aspirin use in the context of recent recommendations. The risk of bleeding has been observed to significantly rise, although large randomized clinical studies have demonstrated a reduction or absence of CVD events. Prevention strategies for cardiovascular disease with low-dose aspirin are no longer advised for persons at intermediate risk. To determine whether taking aspirin is worth the potential dangers, the benefits must be evaluated.Copyright © 2022 Novyi Russkii Universitet. All rights reserved.
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At the beginning of 2020, a pandemic of a novel coronavirus infection was declared in the world. Since the beginning of the pandemic, the search for drugs for etiotropic therapy as the basis for the treatment of the infectious process has begun. The review provides data on the application points of antiviral activity of drugs, taking into account the life cycle of the etiological agent - the SARS-CoV-2 virus. The mechanisms of drug action on RNA-dependent RNA polymerase (molnupiravir, remdesivir, favipiravir) and protease (nirmatrelvir together with ritonavir) SARS-CoV-2 are described. Among of outpatient patients at risk, the use of molnupiravir up to 5 days from the onset of the disease provided a 30% reduction in the risk of hospitalization and an 89% reduction in the risk of death. The use of a 10-day course of remdesivir in inpatient patients led to a reduction in the duration of clinical manifestations by 5 days, and the use of the drug for 3 days on an outpatient basis had a beneficial effect on a group of high-risk patients in the form of a reduction in the risk of hospitalization and death by 87%. Among outpatient patients using favipiravir, the onset of clinical improvement was noted 4 days earlier compared to the control group. The administration of nirmatrelvir in combination with ritonavir on an outpatient basis led to an 89% reduction in the risk of hospitalization or death. The molecular basis and principles of the use of blocking monoclonal antibodies as a fundamentally new group of biological drugs for etiotropic therapy are discussed. Information is provided on the effects of drugs on alpha, beta, gamma, delta and omicron variants of the virus. The profile of drug-drug interaction of drugs and basic therapy is analyzed. Early initiation of etiotropic therapy on an outpatient regime provides a more favorable course of the disease, which is characterized by a shorter duration of clinical manifestations, a reduced risk of hospitalization and the onset of death.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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COVID-19 is a disease caused by SARS-CoV-2 that can trigger respiratory tract infection. Due to its tendency to affect the upper respiratory tract (sinuses, nose and throat) or lower respiratory tract (windpipe and lungs), this disease is life-threatening and affects a large number of populations. This virus's unique and complex nature enhances the scope to look into the direction of herbal plants and their constituents for its prevention and treatment. The herbal remedies can have preventive as well as therapeutic actions. This review focuses on various aspects of using herbal medicines for COVID-19, as herbal constituents may also have adverse effects. Various studies revealed that some medicinal plants show life-threatening adverse effects, so selecting plants, and their related studies should be appropriate and strategic. This article includes various factors that should be considered before herbal drug use in COVID-19 patients. These are clinical trials, safety, molecular mechanism, and self-medication, which have been elaborated. This article also discusses the targets of covid-19 and different coronavirus strains. As before, treatment diagnosis of the disease is very important. Various patents have been filed and granted for its proper diagnosis so that its treatment can be easy.Copyright © 2022 Society of Pharmaceutical Sciences and Research. All rights reserved.
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Influenza and coronavirus infections are especially dangerous due to being capable of causing pandemics and clinical complications in the nervous and cardiovascular systems, as well as exacerbation of chronic diseases (diabetes mellitus, heart failure, chronic obstructive bronchopneumonia, etc.), which can cause delayed death, especially in children under two years of age, the elderly, and individuals with poor health. The aim of the study was to search for compounds effective against these two topical viruses which possess constant epidemic activity - influenza virus and betacoronavirus - among new adamantane derivatives containing a NO-donor fragment or a dopamine residue. Another purpose of the study was determination of cytotoxicity and antiviral activity of compounds on cell lines permissive for influenza virus and betacoronavirus. The antiviral activity of 6 adamantane derivatives against strains of the influenza virus (H1N1) and betacoronavirus was studied. It was established that the NO-donor derivative of aminoadamantane succinate and the dopamine derivative of adamantanebenzoic acid had the greatest ability to suppress the development of the influenza virus with a chemotherapeutic index above 60. No promising compounds against betacoronavirus were identified.Copyright © Team of Authors, 2022.
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Since the outbreak of the novel coronavirus (SARS-CoV-2) disease COVID-19 (also known as 2019-nCoV) caused by SARS-CoV-2 in the end of 2019, it has spread rapidly in worldwide. Besides developing effective vaccines, it is urgent to develop safe and effective anti-SARS-CoV-2 drugs to fight this disease. Paxlovid, molnupiravir, sotrovimab and bebtelovimab are urgently authorized by FDA have been proved to be effective against Omicron. This manuscript mainly reviews the recent progress of effective inhibitors against the virus in the world, including receptor inhibitors, antibodies, natural product inhibitors, synthetic inhibitors and broad-spectrum antiviral drugs that are effective against other RNA viruses. © 2023, Chinese Pharmaceutical Association. All rights reserved.
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Ethnopharmacological relevance: Several studies have confirmed that intestinal microflora dysbiosis correlates with the severity of COVID-19 patients. Clinical meta-analysis and our data show that the circulating miRNAs like miRNA-146 and the levels of serum cytokines in the peripheral blood are closely related to mild to moderate COVID-19 patients. Despite the widespread use of traditional herbal medicine for COVID-19 in China, the mechanisms remain largely uncovered. Aim of the study: We conducted an observational case-control study to verify the efficacy and safety of traditional Chinese herbal medicine Qushi Jianpi Hewei Decoction (QJHD) for mild to moderate COVID-19 patients, and investigated the potential biomolecular mechanisms through metagenomics and transcriptomic sequencing methods. Material(s) and Method(s): QJHD was given orally twice a day individually for 14 to 28 days. A total of 10 patients were enrolled in the study and given QJHD. We observed advantages in clinical cure time rate, and the relief of gastrointestinal symptoms as compared with reports in the literature. The metagenomics sequencing data of fecal microflora and transcriptomic sequencing data of blood cell in patients with SARS-Cov-2 infection patients were selected compared to the healthy control donors. Result(s): No serious adverse events were reported. Meanwhile, the transcriptome analysis showed a decrease of the hsa-miR-21-5p expression in peripheral blood without QJHD. The species composition analysis showed an increase in the expression of Faecalibacterium prausnitzii in the intestinal tract;The interleukin-10 (IL-10) expression also in COVID-19 patient decreased in peripheral blood compared with healthy control donors. And we found an improvement in these parameters in patients taking QJHD. Conclusion(s): Our findings show that QJHD could improve clinical outcomes of mild to moderate COVID-19 patients, probably through beneficial immunomodulatory effects by regulating Faecalibacterium prausnitzii in the intestinal tract and hsa-miR-21 and IL-10 expression in peripheral blood. (chictr.org.cn, ChiCTR2000030305)Copyright © 2022 The Author(s)