Antiviral therapy of COVID-19

The COVID-19 pandemic required rapid response to the needs of critically ill patients, and one of the solutions was re-purposing of drugs with wide spectrum of antiviral action for treatment of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. The re-purposing characteristically started with outof-label use in single or series of cases, to continue after the first promising results with randomised clinical trials. There are several drugs that are currently tested in ongoing clinical trials: antimalarials hydroxychloroquine and chloroquine, HIV protease inhibitors lopinavir/ritonavir, broad spectrum antivirals umifenovir (anti-influenza drug) and favipiravir, antiparasitary drug ivermectin and nucleotide analogue remdesivir. However, up to date only a few trials are completed and published, precluding definitive conclusions about efficacy and safety of these drugs. Until major clinical trials are completed, physicians who decide to use these drugs out-of-label should properly inform their patients of all potential risks and benefits and seek for their consent before administration of the drugs.

Download Full-text

Current Potential Therapeutic Approaches against SARS-CoV-2: A Review

Biomedicines ◽

10.3390/biomedicines9111620 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1620

Author(s):

Dharmendra Kumar Yadav ◽

Desh Deepak Singh ◽

Ihn Han ◽

Yogesh Kumar ◽

Eun-Ha Choi

Keyword(s):

Wide Spectrum ◽

Host Cells ◽

Hiv Protease ◽

Hiv Protease Inhibitors ◽

Therapeutic Approaches ◽

S Protein ◽

Angiotensin Converting Enzyme 2 ◽

Nucleotide Analogue ◽

Infection Treatment ◽

Current Potential

The ongoing SARS-CoV-2 pandemic is a serious threat to public health worldwide and, to date, no effective treatment is available. Thus, we herein review the pharmaceutical approaches to SARS-CoV-2 infection treatment. Numerous candidate medicines that can prevent SARS-CoV-2 infection and replication have been proposed. These medicines include inhibitors of serine protease TMPRSS2 and angiotensin converting enzyme 2 (ACE2). The S protein of SARS-CoV-2 binds to the receptor in host cells. ACE2 inhibitors block TMPRSS2 and S protein priming, thus preventing SARS-CoV-2 entry to host cells. Moreover, antiviral medicines (including the nucleotide analogue remdesivir, the HIV protease inhibitors lopinavir and ritonavir, and wide-spectrum antiviral antibiotics arbidol and favipiravir) have been shown to reduce the dissemination of SARS-CoV-2 as well as morbidity and mortality associated with COVID-19.

Download Full-text

Impact of Attending a Healthcare Conference in Toronto During the Severe Acute Respiratory Syndrome Crisis: Survey of Delegates

Pain Research and Management ◽

10.1155/2004/131786 ◽

2004 ◽

Vol 9 (3) ◽

pp. 137-143 ◽

Cited By ~ 1

Author(s):

Jennifer Stinson ◽

Colin JL McCartney ◽

Andrea Leung ◽

Joel Katz

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Health Care Professionals ◽

Survey Design ◽

Minimal Risk ◽

Prospective Survey ◽

Risks And Benefits ◽

Potential Risks ◽

Level Of Concern ◽

The Impact ◽

Screening Measures

OBJECTIVE:To describe the impact on delegates of attending the Canadian Pain Society's annual meeting in Toronto during the severe acute respiratory syndrome (SARS) crisis in May 2003.METHODS:A prospective survey design was used. Surveys were sent to all delegates (n=432) who attended the conference, and 294 delegates responded (68% response rate). The survey was developed to determine the level of concern about travelling to Toronto; the adequacy of screening measures; the level of stress about attending; and the occupational consequences of attending.RESULTS:Fifty per cent of the participants were not concerned about travelling to Toronto, while the other 50% expressed some concern ranging from mild to serious. Concerns included being exposed to SARS and fear of transmitting it to others upon return. Reasons for attending the conference despite concern included a desire for continuing education, decrease in the number of reported SARS cases, and perceived minimal risk. Almost one-half (n=140) felt the screening measures at the conference were adequate, while 4% felt they were inadequate and 9% somewhat adequate. Delegates (n=99) suggested that temperature-taking (32.2%), improved screening vigilance (14.4%), SARS screening forms checked daily (9.1%), strictly controlled entry (8.1%) and adopting hospital screening procedures (7.1%) should have been instituted.CONCLUSION:Health care professionals planning conferences in this era of new respiratory diseases can benefit from understanding the responses of delegates who attended conferences during outbreaks. Clear communication about the potential risks and benefits, as well as instituting full screening precautions, will help to allay concerns.

Download Full-text

Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

Marine Drugs ◽

10.3390/md18040225 ◽

2020 ◽

Vol 18 (4) ◽

pp. 225 ◽

Cited By ~ 56

Author(s):

Davide Gentile ◽

Vincenzo Patamia ◽

Angela Scala ◽

Maria Teresa Sciortino ◽

Anna Piperno ◽

...

Keyword(s):

Molecular Dynamics ◽

Severe Acute Respiratory Syndrome ◽

Middle Eastern ◽

Pharmacophore Model ◽

Hiv Protease ◽

Marine Natural Product ◽

Computational Techniques ◽

Hiv Protease Inhibitors ◽

Global Public Health ◽

Main Protease

The current emergency due to the worldwide spread of the COVID-19 caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness has not yet been assessed. The main protease (Mpro) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent Mpro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by a hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed this study to highlight some crucial aspects. Seventeen potential SARS-CoV-2 Mpro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

Download Full-text

HIV protease inhibitors saquinavir and nelfinavir are potent inhibitors of cathepsin L activity: A potential treatment for COVID-19 patients

10.21203/rs.3.rs-37258/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Marcelo Freitas Montenegro ◽

Yousef Al-Abed ◽

Mingzhu He ◽

Kevin J. Tracey ◽

Timothy R. Billiar

Keyword(s):

Clinical Trials ◽

Cathepsin L ◽

Inhibitory Effect ◽

Host Cells ◽

Hiv Protease ◽

Hiv Protease Inhibitors ◽

Potential Treatment ◽

Approved Drugs ◽

Fda Approved Drugs

Abstract The 2019 coronavirus disease pandemic (COVID-19) has mobilized efforts worldwide, and several ongoing clinical trials aimed at developing a drug-based treatment for its control. Cathepsin L is an endosomal cysteine protease that mediates the cleavage of the S1 subunit of the coronavirus surface spike glycoprotein. This cleavage is necessary for coronavirus entry into human host cells and viruses/host cell endosome membrane fusion. Therefore, cathepsin L is a potential target for the treatment of COVID-19 patients. In this report, we describe a previously unknown inhibitory effect of two FDA-approved drugs, saquinavir and nelfinavir, on human cathepsin L activity. Whether the pivotal role for cathepsin L in Sars-Cov-2 infection described in vitro can be translated to humans, our results support immediate clinical trials of saquinavir or nelfinavir as a potential treatment for COVID-19 patients.

Download Full-text

HIV protease inhibitors: recent clinical trials and recommendations on use

Expert Opinion on Pharmacotherapy ◽

10.1517/14656560902980202 ◽

2009 ◽

Vol 10 (10) ◽

pp. 1615-1629 ◽

Cited By ~ 24

Author(s):

José Vicente Fernández-Montero ◽

Pablo Barreiro ◽

Vicente Soriano

Keyword(s):

Clinical Trials ◽

Protease Inhibitors ◽

Hiv Protease ◽

Hiv Protease Inhibitors

Download Full-text

Glycoprotein IIb/IIIa inhibitors for the neurointerventionalist

Interventional Neuroradiology ◽

10.1177/15910199211015038 ◽

2021 ◽

pp. 159101992110150

Author(s):

Davide Simonato ◽

Robin J Borchert ◽

Marc-Antoine Labeyrie ◽

Maurizio Fuschi ◽

Lucie Thibault ◽

...

Keyword(s):

Clinical Trials ◽

Large Scale ◽

Antiplatelet Drugs ◽

Risks And Benefits ◽

Hemorrhagic Complications ◽

Potential Risks ◽

Neurointerventional Procedures ◽

Insight Into

Antiplatelet therapies are commonly used in neurointerventional procedures. However, specific guidelines for their use in these settings is lacking and it can often be difficult to balance the potential risks and benefits of these medications. Considering the continued growth and adoption of neurointerventional procedures, it is crucial to understand the properties of these agents in order to use them safely. Large-scale clinical trials are still needed to clarify many of these aspects for this emerging field. However, the existing literature already provides insight into which antiplatelet drugs are of benefit to the neurointerventionalist as well as their associated risks of ischemic and hemorrhagic complications. Hence, this review focuses on the applications of GPIIb/IIIA inhibitors to neurointerventional procedures.

Download Full-text

DOES HEPARIN HAVE AN ESSENTIAL ROLE IN THE TREATMENT OF THE COVID-19 PANDEMIC? A REVIEW

Global Journal of Public Health Medicine ◽

10.37557/gjphm.v3i1.84 ◽

2021 ◽

Vol 3 (1) ◽

pp. 374-385

Keyword(s):

Infectious Disease ◽

Clinical Trials ◽

Severe Acute Respiratory Syndrome ◽

Prothrombin Time ◽

Inflammatory Mediators ◽

Observational Studies ◽

Essential Role ◽

Clinical Manifestations ◽

Efficacy And Safety ◽

Plasma Markers

Coronavirus 2019 (COVID-19), is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first reported in December 2019. The plasma markers of coagulation, like D-dimers and elevated prothrombin time (PT) are higher in patients with COVID-19. The administration of anticoagulant is beneficial in those patients. Heparins have many therapeutic functions that are important for the controlling of COVID-19-associated clinical manifestations like, neutralization of inflammatory mediators and neutralization of extracellular cytotoxic histones. Many observational studies in different countries have been done and large number of clinical trials have been designed and registered to evaluate efficacy and safety of heparin for patients with COVID-19. The aim of this narrative review is to summarize all available data from previously published studies concerning the use of heparin in treatment of the COVID-19 pandemic.

Download Full-text

Challenges of cancer immunotherapy and chemotherapy during the COVID-19 pandemic

Tumori Journal ◽

10.1177/03008916211063939 ◽

2021 ◽

pp. 030089162110639

Author(s):

Mobina Fathi ◽

Kimia Vakili ◽

Kimia Jazi ◽

Mohammad Amin Sadeghi ◽

Mohammadreza Hajiesmaeili ◽

...

Keyword(s):

Systematic Review ◽

High Risk ◽

Cancer Therapy ◽

Patient Monitoring ◽

Malignant Tumors ◽

Efficacy And Safety ◽

Cancer Treatments ◽

Cancer Management ◽

Risks And Benefits ◽

Potential Risks

People at high risk of morbidity and mortality from coronavirus disease 2019 (COVID-19), including patients dealing with malignancies and patients on immunosuppressive anticancer therapies, need to be followed carefully as the pandemic continues. Challenges in continuing cancer management and patient monitoring are of concern given the importance of timing in cancer therapy. Alternative treatment decisions and priorities are also important considerations. The efficacy and safety of various cancer treatments in patients with COVID-19 are other important considerations. In this systematic review, we summarize the potential risks and benefits of cancer treatments applied to patients with COVID-19 and malignant tumors. Using the PubMed and Scopus databases, we reviewed studies involving cancer therapy and COVID-19 to address the recent discoveries and related challenges of cancer therapy in patients with COVID-19 and cancer.

Download Full-text

Repositioning HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors for the treatment of SARS-CoV-2 infection and COVID-19

European Journal of Clinical Pharmacology ◽

10.1007/s00228-021-03108-x ◽

2021 ◽

Author(s):

Nils von Hentig

Keyword(s):

Clinical Trials ◽

Rna Polymerase ◽

Protease Inhibitors ◽

Study Design ◽

Drug Repositioning ◽

Rna Virus ◽

Antiviral Treatment ◽

Hiv Protease ◽

Hiv Protease Inhibitors ◽

Polymerase Inhibitors

Abstract Aims SARS-CoV-2 is a single-stranded RNA virus which is part of the ß-coronavirus family (like SARS 2002 and MERS 2012). The high prevalence of hospitalization and mortality, in addition to the lack of vaccines and therapeutics, forces scientists and clinicians around the world to evaluate new therapeutic options. One strategy is the repositioning of already known drugs, which were approved drugs for other indications. Subject and method SARS-CoV-2 entry inhibitors, RNA polymerase inhibitors, and protease inhibitors seem to be valuable targets of research. At the beginning of the pandemic, the ClinicalTrials.gov webpage listed n=479 clinical trials related to the antiviral treatment of SARS-CoV-2 (01.04.2020, “SARS-CoV-2,” “COVID-19,” “antivirals,” “therapy”), of which n=376 are still accessible online in January 2021 (10.01.2021). Taking into account further studies not listed in the CTG webpage, this narrative review appraises HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors as promising candidates for the treatment of COVID-19. Results Lopinavir/ritonavir, darunavir/cobicistat, remdesivir, tenofovir-disoproxilfumarate, favipriravir, and sofosbuvir are evaluated in clinical studies worldwide. Study designs show a high variability and results often are contradictory. Remdesivir is the drug, which is deployed in nearly 70% of the reviewed clinical trials, followed by lopinavir/ritonavir, favipiravir, ribavirine, and sofosbuvir. Discussion This review discusses the pharmacological/clinical background and questions the rationale and study design of clinical trials with already approved HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors which are repositioned during the SARS-CoV-2 pandemic worldwide. Proposals are made for future study design and drug repositioning of approved antiretroviral compounds.

Download Full-text