Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 3.948
Filter
2.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(5): 1005-1014, 2022 Oct 25.
Article in Chinese | MEDLINE | ID: covidwho-2100336

ABSTRACT

We aim to screen out the active components that may have therapeutic effect on coronavirus disease 2019 (COVID-19) from the severe and critical cases' prescriptions in the "Coronavirus Disease 2019 Diagnosis and Treatment Plan (Trial Ninth Edition)" issued by the National Health Commission of the People's Republic of China and explain its mechanism through the interactions with proteins. The ETCM database and SwissADME database were used to screen the active components contained in 25 traditional Chinese medicines in 3 prescriptions, and the PDB database was used to obtain the crystal structures of 4 proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular docking was performed using Autodock Vina and molecular dynamics simulations were performed using GROMACS. Binding energy results showed that 44 active ingredients including xambioona, gancaonin L, cynaroside, and baicalin showed good binding affinity with multiple targets of SARS-CoV-2, while molecular dynamics simulations analysis showed that xambioona bound more tightly to the nucleocapsid protein of SARS-CoV-2 and exerted a potent inhibitory effect. Modern technical methods are used to study the active components of traditional Chinese medicine and show that xambioona is an effective inhibitor of SARS-CoV-2 nucleocapsid protein, which provides a theoretical basis for the development of new anti-SARS-CoV-2 drugs and their treatment methods.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , SARS-CoV-2 , Molecular Docking Simulation , Medicine, Chinese Traditional , Molecular Dynamics Simulation , Nucleocapsid Proteins , Antiviral Agents/therapeutic use , Antiviral Agents/chemistry , Antiviral Agents/pharmacology
3.
Int J Mol Sci ; 23(21)2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2099581

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world's population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19. In this report, we evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5. Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects. Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Ceramides , COVID-19/drug therapy , Disease Models, Animal , Fluoxetine/pharmacology , Fluoxetine/therapeutic use
4.
Int J Mol Sci ; 23(21)2022 Nov 05.
Article in English | MEDLINE | ID: covidwho-2099579

ABSTRACT

Several human diseases are caused by viruses, including cancer, Type I diabetes, Alzheimer's disease, and hepatocellular carcinoma. In the past, people have suffered greatly from viral diseases such as polio, mumps, measles, dengue fever, SARS, MERS, AIDS, chikungunya fever, encephalitis, and influenza. Recently, COVID-19 has become a pandemic in most parts of the world. Although vaccines are available to fight the infection, their safety and clinical trial data are still questionable. Social distancing, isolation, the use of sanitizer, and personal productive strategies have been implemented to prevent the spread of the virus. Moreover, the search for a potential therapeutic molecule is ongoing. Based on experiences with outbreaks of SARS and MERS, many research studies reveal the potential of medicinal herbs/plants or chemical compounds extracted from them to counteract the effects of these viral diseases. COVID-19's current status includes a decrease in infection rates as a result of large-scale vaccination program implementation by several countries. But it is still very close and needs to boost people's natural immunity in a cost-effective way through phytomedicines because many underdeveloped countries do not have their own vaccination facilities. In this article, phytomedicines as plant parts or plant-derived metabolites that can affect the entry of a virus or its infectiousness inside hosts are described. Finally, it is concluded that the therapeutic potential of medicinal plants must be analyzed and evaluated entirely in the control of COVID-19 in cases of uncontrollable SARS infection.


Subject(s)
COVID-19 , Plants, Medicinal , Virus Diseases , Humans , COVID-19/drug therapy , COVID-19/epidemiology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Antiviral Agents/chemistry , SARS-CoV-2 , Disease Outbreaks/prevention & control , Virus Diseases/drug therapy , Plants, Medicinal/metabolism
5.
Pharm Biol ; 60(1): 2049-2087, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2097124

ABSTRACT

CONTEXT: The emergence of zoonotic viruses in the last decades culminating with COVID-19 and challenges posed by the resistance of RNA viruses to antiviral drugs requires the development of new antiviral drugs. OBJECTIVE: This review identifies natural products isolated from Asian and Pacific medicinal plants with in vitro and in vivo antiviral activity towards RNA viruses and analyses their distribution, molecular weights, solubility and modes of action. MATERIALS AND METHODS: All data in this review was compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem and library search from 1961 to 2022. RESULTS: Out of about 350 molecules identified, 43 phenolics, 31 alkaloids, and 28 terpenes were very strongly active against at least one type of RNA virus. These natural products are mainly planar and amphiphilic, with a molecular mass between 200 and 400 g/mol and target viral genome replication. Hydroxytyrosol, silvestrol, lycorine, tylophorine and 12-O-tetradecanoylphorbol 13-acetate with IC50 below 0.01 µg/mL and selectivity index (S.I.) above 100 have the potential to be used for the development of anti-RNA virus leads. DISCUSSION AND CONCLUSIONS: The medicinal plants of Asia and the Pacific are a rich source of natural products with the potential to be developed as lead for the treatment of RNA viral infections.


Subject(s)
Biological Products , COVID-19 , Plants, Medicinal , RNA Viruses , Biological Products/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use
6.
Rev Esp Quimioter ; 35 Suppl 3: 10-15, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2091722

ABSTRACT

The use of antiviral drugs represents an important progress in the therapeutic management of COVID-19, leading to a substantial reduction of SARS-CoV-2-related complications and mortality. In immunocompetent host, peak viral replication occurs around the symptom's onset, and it prolongs for 5 to 7 days that is the window of opportunity for giving an antiviral. Accordingly, early and rapid diagnostic of the infection in the outpatient clinic is essential as well as the availability of oral agents that can be easily prescribe. Remdesivir has demonstrated its efficacy in hospitalized patients requiring oxygen support and in mild/moderate cases to avoid the hospitalization, however, the intravenous administration limits its use among outpatients. Molnupiravir and nirmatrelvir/ritonavir are potent oral antiviral agents. In the present review we discuss the potential targets against SARS-CoV-2, and an overview of the main characteristics and clinical results with the available antiviral agents for the treatment of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Ritonavir/therapeutic use , Oxygen
7.
Rev Esp Quimioter ; 35 Suppl 3: 2-5, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2091720

ABSTRACT

SARS-CoV-2 infection now seems to have entered the announced endemic phase. The population's immunity is increasingly more robust, thanks to successive vaccination and booster campaigns, and the almost inevitable exposure and re-exposure to the virus itself, which has truly served as a natural immunizing mechanism. On the other hand, the genetic drift of the virus is leading it to become another catarrhal agent, as are the other endemic human coronaviruses. However, it should not be lost sight of that there are still segments of the population with susceptibility to severe COVID, who will be candidates to continue receiving vaccine boosters or antiviral drugs in the initial stages of infection.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , COVID-19 Vaccines , Antiviral Agents/therapeutic use , Vaccination
8.
MMWR Morb Mortal Wkly Rep ; 71(43): 1384-1385, 2022 Oct 28.
Article in English | MEDLINE | ID: covidwho-2091067

ABSTRACT

Equitable access to COVID-19 therapeutics is a critical aspect of the distribution program led by the U.S. Department of Health and Human Services (HHS).* Two oral antiviral products, nirmatrelvir/ritonavir (Paxlovid)† and molnupiravir (Lagevrio),§ received emergency use authorization (EUA) from the Food and Drug Administration (FDA) in December 2021, to reduce the risk for COVID-19-associated hospitalization and death for those patients with mild to moderate COVID-19 who are at higher risk for severe illness (1,2). HHS has been distributing these medications at no cost to recipients since their authorization. Data collected from provider sites during December 23, 2021-May 21, 2022, indicated substantial disparities in the population-adjusted dispensing rates in high social vulnerability (high-vulnerability) zip codes compared with those in medium- and low-vulnerability zip codes (3). Specifically, dispensing rates for the 4-week period during April 24-May 21, 2022, were 122 per 100,000 residents (19% of overall population-adjusted dispensing rates) in high-vulnerability zip codes compared with 247 (42%) in medium-vulnerability and 274 (39%) in low-vulnerability zip codes. This report provides an updated analysis of dispensing rates by zip code-level social vulnerability and highlights important intervention strategies.


Subject(s)
COVID-19 , United States/epidemiology , Humans , COVID-19/drug therapy , Antiviral Agents/therapeutic use , Social Vulnerability , Ritonavir , Hospitalization
9.
Med J Aust ; 217 Suppl 9: S7-S13, 2022 Nov 06.
Article in English | MEDLINE | ID: covidwho-2090766

ABSTRACT

Early treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can prevent hospitalisation and death in patients with coronavirus disease 2019 (COVID-19) who have one or more risk factors for serious COVID-19 progression. While early treatment presents a range of logistical challenges, clinicians are nevertheless aided by a growing number of approved medications for early treatment of COVID-19. Medications include drugs that inhibit SARS-CoV-2 viral replication, anti-SARS-CoV-2 monoclonal antibody formulations that provide passive immunisation, and immunomodulatory drugs that suppress the body's inflammatory response. Several drugs with different modes of action are approved in Australia for early treatment of COVID-19, including nirmatrelvir plus ritonavir, molnupiravir, and monoclonal antibody formulations. Although these drugs are recommended, clinicians are encouraged to remain up to date on current indications, contraindications and the clinical efficacy of these drugs against SARS-CoV-2 variants currently circulating in communities. Other treatments, including hydroxychloroquine, ivermectin and dietary supplements, have been popularised but are not recommended for early treatment of COVID-19. As new drugs and new data on use of existing approved drugs become available, clinicians face a growing challenge in determining the optimal treatments from the array of options. As it stands, early treatment of COVID-19 needs to be individualised depending on age, pregnancy status, existing medications, and renal and liver disease status. Future treatments in development might have roles in patients with lower risk profiles and in reducing transmission as we learn to live with SARS-CoV-2.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Humans , Pregnancy , Female , SARS-CoV-2 , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Antibodies, Viral , Antibodies, Monoclonal , Antiviral Agents/therapeutic use
10.
Antivir Chem Chemother ; 30: 20402066221130853, 2022.
Article in English | MEDLINE | ID: covidwho-2089137

ABSTRACT

As a result of the multiple gathering and travels restrictions during the SARS-CoV-2 pandemic, the annual meeting of the International Society for Antiviral Research (ISAR), the International Conference on Antiviral Research (ICAR), could not be held in person in 2021. Nonetheless, ISAR successfully organized a remote conference, retaining the most critical aspects of all ICARs, a collegiate gathering of researchers in academia, industry, government and non-governmental institutions working to develop, identify, and evaluate effective antiviral therapy for the benefit of all human beings. This article highlights the 2021 remote meeting, which presented the advances and objectives of antiviral and vaccine discovery, research, and development. The meeting resulted in a dynamic and effective exchange of ideas and information, positively impacting the prompt progress towards new and effective prophylaxis and therapeutics.


Subject(s)
Antiviral Agents , COVID-19 , Humans , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , SARS-CoV-2 , COVID-19/drug therapy , Pandemics
11.
Antimicrob Agents Chemother ; 66(11): e0122922, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2088397

ABSTRACT

Nirmatrelvir/ritonavir is an effective antiviral therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Use is not recommended in patients with end-stage renal disease (ESDR) due to a lack of data. We investigated the pharmacokinetics of nirmatrelvir/ritonavir (150 mg/100 mg twice a day) in four patients with ESRD undergoing hemodialysis. Nirmatrelvir peak concentrations ranged from 4,563 to 7,898 ng/mL and declined after hemodialysis. Concentrations were up to 4-fold higher but still within the range known from patients without ESRD, without accumulation of nirmatrelvir after the end of treatment.


Subject(s)
COVID-19 , Kidney Failure, Chronic , Humans , Ritonavir/therapeutic use , COVID-19/drug therapy , SARS-CoV-2 , Kidney Failure, Chronic/drug therapy , Renal Dialysis , Antiviral Agents/therapeutic use
12.
J Med Chem ; 64(24): 17601-17626, 2021 12 23.
Article in English | MEDLINE | ID: covidwho-2084518

ABSTRACT

Nucleic acid aptamers are single-stranded DNA or RNA molecules selected in vitro that can bind to a broad range of targets with high affinity and specificity. As promising alternatives to conventional anti-infective agents, aptamers have gradually revealed their potential in the combat against infectious diseases. This article provides an overview on the state-of-art of aptamer-based antibacterial and antiviral therapeutic strategies. Diverse aptamers targeting pathogen-related components or whole pathogenic cells are summarized according to the species of microorganisms. These aptamers exhibited remarkable in vitro and/or in vivo inhibitory effect for pathogenic invasion, enzymatic activities, or viral replication, even for some highly drug-resistant strains and biofilms. Aptamer-mediated drug delivery and controlled drug release strategies are also included herein. Critical technical barriers of therapeutic aptamers are briefly discussed, followed by some future perspectives for their implementation into clinical utility.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Aptamers, Nucleotide/therapeutic use , Communicable Diseases/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Antiviral Agents/chemistry , Aptamers, Nucleotide/chemistry , Biofilms , Humans , Structure-Activity Relationship
14.
Intern Med ; 61(20): 3017-3028, 2022 Oct 15.
Article in English | MEDLINE | ID: covidwho-2079919

ABSTRACT

Objective This retrospective, single-center study assessed the effects of interferon (IFN)-free treatment of hepatitis C virus (HCV) infection, which has been approved for seven years; calculated the incidence of hepatocellular carcinoma (HCC) after achieving a sustained virologic response (SVR); and elucidated problems with follow-up for surveillance of post-SVR HCC, particularly the impact of the coronavirus disease 2019 (COVID-19) pandemic. Methods We summarized the SVR achievement rate of 286 HCV-infected patients who received 301 IFN-free treatments and analyzed the cumulative incidence of initial HCC and the cumulative continuation rate of follow-up after SVR in the 253 patients who achieved SVR and did not have a history of HCC. Results Among 286 patients who received IFN-free treatments, 14 dropped out, and the 272 remaining patients achieved an SVR after receiving up to third-line treatment. Post-SVR HCC occurred in 18 (7.1%) of the 253 patients without a history of HCC, with a cumulative incidence at 3 and 5 years after SVR of 6.6% and 10.0%, respectively; the incidence of cirrhosis at those time points was 18.2% and 24.6%, respectively.Of the 253 patients analyzed, 58 (22.9%) discontinued follow-up after SVR. Patients who had no experience with IFN-based therapy tended to drop out after SVR. Notably, the number of dropouts per month has increased since the start of the pandemic. Conclusion Currently, IFN-free treatment is showing great efficacy. However, the incidence of HCC after SVR should continue to be monitored. In this study, the COVID-19 pandemic did not affect treatment outcomes, but it may affect surveillance for post-SVR HCC.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Liver Neoplasms , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/virology , Hepacivirus , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Interferons/therapeutic use , Liver Neoplasms/epidemiology , Liver Neoplasms/virology , Patient Dropouts , Retrospective Studies , Sustained Virologic Response
15.
PLoS One ; 17(10): e0275181, 2022.
Article in English | MEDLINE | ID: covidwho-2079742

ABSTRACT

BACKGROUND: Glycyrrhizin, an active component of liquorice root extract, exhibits antiviral and immunomodulatory properties by direct inhibition of the pro-inflammatory alarmin HMGB1 (High-mobility group box 1). OBJECTIVE: The aim of this study was to explore the role of liquorice intake on the viral entry receptor ACE2 (angiotensin-converting enzyme 2) and the immunoregulatory HMGB1 in healthy individuals and to explore HMGB1 expression in coronavirus disease 2019 (COVID-19) or non-COVID-19 in ARDS (acute respiratory distress syndrome patients). MATERIAL AND METHODS: This study enrolled 43 individuals, including hospitalised patients with i) acute respiratory distress syndrome (ARDS) due to COVID-19 (n = 7) or other underlying causes (n = 12), ii) mild COVID-19 (n = 4) and iii) healthy volunteers (n = 20). Healthy individuals took 50 g of liquorice (containing 3% liquorice root extract) daily for 7 days, while blood samples were collected at baseline and on day 3 and 7. Changes in ACE2 and HMGB1 levels were determined by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Additionally, HMGB1 levels were measured in hospitalised COVID-19 patients with mild disease or COVID-19 associated acute respiratory distress syndrome (ARDS) and compared with a non-COVID-19-ARDS group. RESULTS: Liquorice intake significantly reduced after 7 days both cellular membranous ACE2 expression (-51% compared to baseline levels, p = 0.008) and plasma HMGB1 levels (-17% compared to baseline levels, p<0.001) in healthy individuals. Half of the individuals had a reduction in ACE2 levels of at least 30%. HMGB1 levels in patients with mild COVID-19 and ARDS patients with and without COVID-19 were significantly higher compared with those of healthy individuals (+317%, p = 0.002), but they were not different between COVID-19 and non-COVID-19 ARDS. CONCLUSIONS: Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.


Subject(s)
COVID-19 , Glycyrrhiza , HMGB1 Protein , Respiratory Distress Syndrome , Alarmins , Angiotensin-Converting Enzyme 2 , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Glycyrrhiza/metabolism , Glycyrrhizic Acid/pharmacology , Glycyrrhizic Acid/therapeutic use , HMGB1 Protein/metabolism , Humans , Pilot Projects , Receptors, Virus/metabolism , Respiratory Distress Syndrome/drug therapy
16.
Virol J ; 19(1): 159, 2022 Oct 10.
Article in English | MEDLINE | ID: covidwho-2079511

ABSTRACT

The SARS-CoV-2 virus has been raging globally for over 2 years with no end in sight. It has become clear that this virus possesses enormous genetic plasticity, and it will not be eradicated. Under increasing selective pressure from population immunity, the evolution of SARS-CoV-2 has driven it towards greater infectivity, and evasion of humoral and cellular immunity. Omicron and its expanding army of subvariants and recombinants have impaired vaccine protection and made most antibody drugs obsolete. Antiviral drugs, though presently effective, may select for more resistant strains over time. It may be inevitable, then, that future SARS-CoV-2 variants will be immune to our current virus-directed countermeasures. Thus, to gain control over the virus, we need to adopt a new paradigm in searching for next-generation countermeasures and develop host-directed therapeutics (HDTx) and host-directed antivirals (HDA). Different from the virus-directed countermeasures, HDTx and HDA may offer variant agnostic treatment to reduce the risk and severity of infections. In addition, they may exert more uniform effects against the genetically diverse SARS-CoV-2 quasispecies, thereby diminishing the risk of selecting resistant variants. Some promising HDTx and HDA approaches are summarized here.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , SARS-CoV-2/genetics
17.
BMC Med ; 20(1): 359, 2022 10 21.
Article in English | MEDLINE | ID: covidwho-2079420

ABSTRACT

BACKGROUND: The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5-30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. METHODS: The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. RESULTS: Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. CONCLUSIONS: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.


Subject(s)
Anidulafungin , Bunyaviridae Infections , Virus Diseases , Animals , Mice , Anidulafungin/pharmacology , Anidulafungin/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Bunyaviridae Infections/drug therapy , Clathrin , Receptor, Interferon alpha-beta , SARS-CoV-2 , Viral Proteins , Virus Diseases/drug therapy
18.
BMC Infect Dis ; 22(1): 793, 2022 Oct 20.
Article in English | MEDLINE | ID: covidwho-2079395

ABSTRACT

BACKGROUND: Monoclonal antibodies (mAbs) and antivirals have been approved for early therapy of coronavirus disease (COVID-19), however, in the real-life setting, there are difficulties to prescribe these therapies within few days from symptom onset as recommended, and effectiveness of combined use of these drugs have been hypothesised in most-at-risk patients (such as those immunocompromised) but data supporting this strategy are limited. METHODS: We describe the real-life experience of SARS-CoV-2 antivirals and/or monoclonal antibodies (mAbs) and focus on the hospitalisation rate due to the progression of COVID-19. Clinical results obtained through our risk-stratification algorithm and benefits achieved through a strategic proximity territorial centre are provided. We also report a case series with an in-depth evaluation of SARS-CoV-2 genome in relationship with treatment strategy and clinical evolution of patients. RESULTS: Two hundred eighty-eight patients were analysed; 94/288 (32.6%) patients were treated with mAb monotherapy, 171/288 (59.4%) patients were treated with antivirals, and 23/288 (8%) patients received both mAbs and one antiviral drug. Haematological malignancies were more frequent in patients treated with combination therapy than in the other groups (p = 0.0003). There was a substantial increase in the number of treated patients since the opening of the centre dedicated to early therapies for COVID-19. The provided disease-management and treatment appeared to be effective since 98.6% patients recovered without hospital admission. Moreover, combination therapy with mAbs and antivirals seemed successful because all patients admitted to the hospital for COVID-19 did not receive such therapies, while none of the most-at-risk patients treated with combination therapy were hospitalized or reported adverse events. CONCLUSIONS: A low rate of COVID-19 progression requiring hospital admission was observed in patients included in this study. The dedicated COVID-19 proximity territorial service appeared to strengthen the regional sanitary system, avoiding the overwhelming of other services. Importantly, our results also support early combination therapy: it is possible that this strategy reduces the emergence of escape mutants of SARS-CoV-2, thereby increasing efficacy of early treatment, especially in immunocompromised individuals.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Secondary Prevention , Retrospective Studies , COVID-19/drug therapy , Antiviral Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use
19.
Eur Respir Rev ; 31(166)2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-2079386

ABSTRACT

Respiratory virus infection can cause severe illnesses capable of inducing acute respiratory failure that can progress rapidly to acute respiratory distress syndrome (ARDS). ARDS is related to poor outcomes, especially in individuals with a higher risk of infection, such as the elderly and those with comorbidities, i.e. obesity, asthma, diabetes mellitus and chronic respiratory or cardiovascular disease. Despite this, effective antiviral treatments available for severe viral lung infections are scarce. The coronavirus disease 2019 (COVID-19) pandemic demonstrated that there is also a need to understand the role of airborne transmission of respiratory viruses. Robust evidence supporting this exists, but better comprehension could help implement adequate measures to mitigate respiratory viral infections. In severe viral lung infections, early diagnosis, risk stratification and prognosis are essential in managing patients. Biomarkers can provide reliable, timely and accessible information possibly helpful for clinicians in managing severe lung viral infections. Although respiratory viruses highly impact global health, more research is needed to improve care and prognosis of severe lung viral infections. In this review, we discuss the epidemiology, diagnosis, clinical characteristics, management and prognosis of patients with severe infections due to respiratory viruses.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Viruses , Humans , Aged , SARS-CoV-2 , Antiviral Agents/therapeutic use , Biomarkers
20.
Ann Med ; 54(1): 2856-2860, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2077366

ABSTRACT

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 continues to have a serious impact on public health worldwide. Most patients develop mild to moderate symptoms and recover without requiring special treatment, but up to 15% develop severe (dyspnea, hypoxia, lung involvement) or critical symptoms (respiratory failure, septic shock, thromboembolism, multiorgan dysfunction). Although vaccination is having a substantial impact on case numbers, hospitalizations and deaths, there remains a need for new effective treatments against COVID-19. METHODS: This short review aims at reporting on current therapeutics against SARS-CoV-2 focussing on new drugs authorized in the European Union, describing the treatment strategies and the clinical recommendations for the management of hospitalized and non-hospitalized COVID-19 patients based on the available guidelines for clinical practice. RESULTS: New effective drugs, like antiviral medications and monoclonal antibodies, have been developed as therapy against severe and life-threatening disease courses. Specifically, the European Medicines Agency has authorized two antiviral medicines (nirmatrelvir/ritonavir, remdesivir), supporting also early use of molnupiravir before marketing authorization, and four monoclonal antibodies (regdanvimab, casirivimab/imdevimab, sotrovimab, tixagevimab/cilgavimab). In addition, three drugs (anakinra, tocilizumab, baricitinib) previously authorized for the treatment of rheumatoid arthritis are also available to treat COVID-19. CONCLUSIONS: Recommendations and guidelines for clinical practice should be regularly updated as further evidence becomes available in favour or against specific interventions, to inform all stakeholders involved in the health care of COVID-19 patients both in the community and in the hospital setting, aiming at improving the quality of care and therefore the patient outcome.KEY MESSAGESCOVID-19 has been recognized as a multisystem disorder affecting many body systems; this wide spectrum of clinical patterns made difficult an appropriate choice of treatments able to counteract severe symptoms of the disease and alleviate the burden on the healthcare system.New effective drugs, like antiviral medications and monoclonal antibodies, have been developed and approved by the European Medicines Agency as therapy against severe and life-threatening disease courses.Recommendations and guidelines should be regularly updated as further evidence becomes available in favour or against specific interventions aiming at improving the quality of care and therefore the patient outcome.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , SARS-CoV-2 , Pandemics , Ritonavir , Interleukin 1 Receptor Antagonist Protein , European Union , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , Hospitalization
SELECTION OF CITATIONS
SEARCH DETAIL