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1.
Chem Biol Interact ; 362: 110005, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-1866939
2.
Future Virol ; 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1779884

ABSTRACT

Besides the common symptoms in COVID-19, it has been thought to be a more imperative measure to identify the extraordinary manifestations of the illness, which would be more helpful to improve clinical management. In the current report, a 39-year-old woman and a 44-year-old man showed reactive cervical and preauricular lymphadenopathies, respectively, upon a range of the common symptoms of the disease. Interestingly, none of them showed the symptoms of lower respiratory tract infection as well. Notably, a herpes-like skin lesion was also observed on the right lower eyelid in one of the positive patients.

3.
Phytother Res ; 36(2): 891-898, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1694652

ABSTRACT

Colchicine has shown clinical benefits in the management of COVID-19 via its anti-inflammatory effect. However, the exact role of colchicine in COVID-19 patients is unknown. The current clinical trial was performed on 202 patients with moderate to severe COVID-19. Patients were randomly assigned in a 1:1 ratio to receive up to a 3-day course of 0.5 mg colchicine followed by a 12-day course of 1 mg colchicine in combination with standard care or a 15-day course of standard care. Among 202 randomized patients, 153 completed the study and received colchicine/standard care or continued standard care (M age, 54.72 [SD, 15.03] years; 93 [63.1%] men). On day 14, patients in the colchicine/standard care group had significantly higher odds of a better clinical status distribution on chest CT evaluation (p = .048). Based on NYHA classification, the percentage change of dyspnea on day 14 between groups was statistically significant (p = .026), indicating a mean of 31.94% change in the intervention group when compared with 19.95% in the control group. According to this study, colchicine can improve clinical outcomes and reduce pulmonary infiltration in COVID-19 patients if contraindications and precautions are considered and it is prescribed at the right time and in appropriate cases.


Subject(s)
COVID-19 , Colchicine/adverse effects , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Treatment Outcome
4.
Pharmacol Rep ; 74(2): 425-430, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1627165

ABSTRACT

Currently, the world is facing a pandemic of the new coronavirus SARS-CoV-2 that causes COVID-19. Identifying key targets in the viral infection lifecycle is urgently needed for designing therapeutic strategies to combat the virus. Furin is a subtilisin-like proprotein convertase with diverse cellular functions. Emerging evidence suggests that furin plays a critical role in the activation and/or infectivity of SARS-CoV-2. In this perspective, we discuss the potential role of furin in the entry SARS-CoV-2 into host cells. Furthermore, we evaluate available peptide and non-peptide furin inhibitors and potential outcomes, including immune responses.


Subject(s)
COVID-19 , Furin , COVID-19/drug therapy , Humans , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
5.
Comb Chem High Throughput Screen ; 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1547091

ABSTRACT

Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes acute inflammation due to extensive replication of the virus in the epithelial cells of the upper and lower respiratory system. The mammalian target of rapamycin (mTOR) is a l signalling protein with critical functions in cell growth, metabolism, and proliferation. It is known for its regulatory functions in protein synthesis and angiogenesis cascades. The structure of mTOR consists of two distinct complexes (mTORC1 and mTORC2) with diverse functions at different levels of the signaling pathway. By activating mRNA translation, the mTORC1 plays a key role in regulating protein synthesis and cellular growth. On the other hand, the functions of mTORC2 are mainly associated with cell proliferation and survival. By using an appropriate inhibitor at the right time, mTOR modulation could provide immunosuppressive opportunities as antirejection regimens in organ transplantation as well as in the treatment of autoimmune diseases and solid tumours. The mTOR has an important role in the inflammatory process, too. Inhibitors of mTOR might indeed be promising agents in the treatment of viral infections. They have further been successfully used in patients with severe influenza A/H1N1 pneumonia and acute respiratory failure. The officially accepted mTOR inhibitors that have undergone clinical testing are sirolimus, everolimus, temsirolimus, and tacrolimus. Thus, further studies on mTOR inhibitors for SARS-CoV-2 infection or COVID-19 therapy are well merited.

6.
Mol Biol Rep ; 48(12): 8221-8225, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1525563

ABSTRACT

Arglabin (l(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),ll(13)-dien-6,12-olide), is a natural sesquiterpene γ-lactone which was first isolated from Artemisia glabella. The compound has been shown to possess anti-inflammatory activity through inhibition of the NLR Family pyrin domain-containing 3 (NLRP3) inflammasome and production of proinflammatory cytokines including interleukin (IL)-1ß and IL-18. A more hydrophilic derivative of the compound also exhibited antitumor activity in the breast, colon, ovarian, and lung cancer. Some other synthetic derivatives of the compound have also been synthesized with antitumor, cytotoxic, antibacterial, and antifungal activities. Since both NLRP3 inflammasome and cytokine storm are associated with the pathogenesis of COVID-19 and its lethality, compounds like arglabin might have therapeutic potential to attenuate the inflammasome-induced acute respiratory distress syndrome and/or the cytokine storm associated with COVID-19.


Subject(s)
COVID-19/drug therapy , SARS-CoV-2/drug effects , Sesquiterpenes, Guaiane/therapeutic use , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Artemisia , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , Cytokines , Humans , Inflammasomes/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pandemics , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2/pathogenicity , Sesquiterpenes, Guaiane/chemistry , Sesquiterpenes, Guaiane/metabolism , Signal Transduction/drug effects
7.
Int Immunopharmacol ; 101(Pt B): 108257, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1466420

ABSTRACT

Recently, the medications used for the severe form of the coronavirus disease-19 (COVID-19) therapy are of particular interest. In this sense, it has been supposed that anti-VEGF compounds would be good candidates in the face of "cytokine storm" and intussuscepted angiogenesis due to having an appreciable anti-inflammatory effect. Therefore, they can be subjected to therapeutic protocols to manage acute respiratory distress syndrome (ARDS). Since the compelling evidence emphasized that VEGFs contribute to the inflammatory process and play a mainstay role in disease pathogenesis, in this review, we aimed to highlight the VEGF's plausible participation in the cytokine storm exacerbation in COVID-19. Next, the recent clinical advances regarding the anti-VEGF medications, including humanized monoclonal antibody, immunosuppressant, a tyrosine kinase inhibitor, and a cytokine inhibitor, have been addressed in the setting of COVID-19 treatment in critically ill patients. Together, retrieving the increased level of VEGF subsets, as well as antagonizing VEGF related receptors, could be helpful for the treatment of COVID-19, especially in those suffering from ARDS.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , COVID-19/drug therapy , Vascular Endothelial Growth Factors/antagonists & inhibitors , COVID-19/immunology , Critical Illness , Humans , Receptors, Vascular Endothelial Growth Factor/immunology , Vascular Endothelial Growth Factors/immunology
8.
BMC Infect Dis ; 21(1): 297, 2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1150391

ABSTRACT

BACKGROUND: Levamisole has shown clinical benefits in the management of COVID-19 via its immunomodulatory effect. However, the exact role of Levamisole effect in clinical status of COVID-19 patients is unknown. We aimed to evaluate the efficacy of Levamisole on clinical status of patients with COVID-19 during their course of the disease. METHODS: This prospective, double-blind, randomized controlled clinical trial was performed in adult patients with mild to moderate COVID-19 (room-air oxygen saturation > 94%) from late April 2020 to mid-August 2020. Patients were randomly assigned to receive a 3-day course of Levamisole or placebo in combination with routine standard of care. RESULTS: With 25 patients in each arm, 50 patients with COVID-19 were enrolled in the study. Most of the study participants were men (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution when compared to the placebo group (P-value = 0.034 and 0.005, respectively). Moreover, there was significant differences between the two groups in dyspnea at follow-up intervals of 7 (P-value = 0.015) and 14 (P-value = 0.010) days after receiving the interventions. However, no significant difference in fever status was observed on days 1, 3, 7, and 14 in both groups (P-value > 0.05). CONCLUSION: The results of the current study suggest that Levamisole may improve most of clinical status of patients with COVID-19. The patients receiving Levamisole had significantly better chance of clinical status including cough and dyspnea on day 14 when compared to the placebo. However, the effect-size of this finding has uncertain clinical importance. TRIAL REGISTRATION: The trial was registered as IRCT20190810044500N7 (19/09/2020).


Subject(s)
COVID-19/drug therapy , Levamisole/therapeutic use , Adult , Double-Blind Method , Female , Humans , Male , Middle Aged , Prospective Studies , Time Factors , Treatment Outcome , Young Adult
9.
Arch Med Res ; 51(7): 631-635, 2020 10.
Article in English | MEDLINE | ID: covidwho-1023470

ABSTRACT

The novel coronavirus 2019-nCoV (SARS-CoV-2) infection that emerged in China in December 2019 has rapidly spread to become a global pandemic. This article summarizes the potential benefits of erythropoietin (EPO) in alleviating SARS-CoV-2 pathogenesis which is now called COVID-19. As with other coronavirus infection, the lethality of COVID-19 is associated with respiratory dysfunction due to overexpression of proinflammatory cytokines induced by the host immune responses. The resulting cytokine storm leads to the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Erythropoietin, well known for its role in the regulation of erythropoiesis, may have protective effects against ALI/ARDS induced by viral and other pathogens. EPO exerts antiapoptotic and cytoprotective properties under various pathological conditions. With a high safety profile, EPO promotes the production of endothelial progenitor cells and reduce inflammatory processes through inhibition of the nuclear factor-κB (NF-κB) and JAK-STAT3 signaling pathways. Thus, it may be considered as a safe drug candidate for COVID-19 patients if given at the early stage of the disease. The potential effects of erythropoietin on different aspects of ALI/ARDS associated with SARS-CoV-2 infection are reviewed.


Subject(s)
Acute Lung Injury , Anti-Inflammatory Agents/therapeutic use , COVID-19 , Erythropoietin/therapeutic use , Respiratory Distress Syndrome , Acute Lung Injury/drug therapy , Acute Lung Injury/virology , COVID-19/complications , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Humans , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2
10.
Arch Med Res ; 51(7): 733-735, 2020 10.
Article in English | MEDLINE | ID: covidwho-1023461

ABSTRACT

The discovery of new drugs for treating the new coronavirus (SARS-CoV-2) or repurposing those already in use for other viral infections is possible through understanding of the viral replication cycle and pathogenicity. This article highlights the advantage of targeting one of the non-structural proteins, helicase (nsp13), over other SARS-CoV-2 proteins. Highlighting the experience gained from targeting Nsp13 in similar coronaviruses (SARS-CoV and MERS) and known inhibitors, the article calls for research on helicase inhibitors as potential COVID-19 therapy.


Subject(s)
Antiviral Agents , COVID-19 , Enzyme Inhibitors , RNA Helicases/antagonists & inhibitors , SARS-CoV-2 , COVID-19/drug therapy , COVID-19/virology , Humans , Methyltransferases/antagonists & inhibitors , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Viral Nonstructural Proteins/antagonists & inhibitors
13.
Eur J Pharmacol ; 887: 173568, 2020 Nov 15.
Article in English | MEDLINE | ID: covidwho-778808

ABSTRACT

In December 2019, an unprecedented outbreak of pneumonia associated with a novel coronavirus disease 2019 (COVID-19) emerged in Wuhan City, Hubei province, China. The virus that caused the disease was officially named by the World Health Organization (WHO) as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the high transmission rate of SARS-CoV-2, it became a global pandemic and public health emergency within few months. Since SARS-CoV-2 is genetically 80% homologous with the SARS-CoVs family, it is hypothesized that medications developed for the treatment of SARS-CoVs may be useful in the control and management of SARS-CoV-2. In this regard, some medication being tested in clinical trials and in vitro studies include anti-viral RNA polymerase inhibitors, HIV-protease inhibitors, anti-inflammatory agents, angiotensin converting enzyme type 2 (ACE 2) blockers, and some other novel medications. In this communication, we reviewed the general characteristics of medications, medical usage, mechanism of action, as well as SARS-CoV-2 related trials.


Subject(s)
Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19 , Chloroquine/analogs & derivatives , Chloroquine/therapeutic use , DNA-Directed RNA Polymerases/antagonists & inhibitors , Humans , Pandemics
15.
Eur J Pharmacol ; 887: 173530, 2020 Nov 15.
Article in English | MEDLINE | ID: covidwho-738842

ABSTRACT

The global impact of the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infection that caused COVID-19 has been evident in the last few months from the unprecedented socioeconomic disruption to more than 600,000 deaths. The lack of vaccine and effective therapeutic agents for the disease prompted world-wide effort to test those antiviral therapeutics already in use for other diseases. Another interesting approach has been based on the pathological sequel of the disease that involve severe inflammatory reaction (or the cytokine storm) associated with pneumonia in critically ill patients. This article outlines the prophylaxis therapeutic potential of supplements vitamins and micronutrients in COVID-19. By ameliorating the inflammatory and oxidative stress associated with the disease and some direct antiviral effects, the application of these agents as adjuvants and other alternative approaches are discussed. Available clinical trials including those currently registered on these supplements are scrutinized.


Subject(s)
Coronavirus Infections/therapy , Dietary Supplements , Pneumonia, Viral/therapy , Animals , Antioxidants/therapeutic use , COVID-19 , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Vitamins/therapeutic use
16.
J Clin Pharm Ther ; 45(6): 1515-1519, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-733228

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: This article summarizes the effects of sivelestat on acute lung injury/acute respiratory distress syndrome (ALI/ARDS) or ARDS with coagulopathy, both of which are frequently seen in patients with COVID-19. COMMENT: COVID-19 patients are more susceptible to thromboembolic events, including disseminated intravascular coagulation (DIC). Various studies have emphasized the role of neutrophil elastase (NE) in the development of DIC in patients with ARDS and sepsis. It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of injuries in alveolar epithelium and vascular endothelium, as well as reversing the neutrophil-mediated increased vascular permeability. WHAT IS NEW AND CONCLUSIONS: Sivelestat, a selective NE inhibitor, has not been evaluated for its possible therapeutic effects against SARS-CoV-2 infection. Based on its promising beneficial effects in underlying complications of COVID-19, sivelestat could be considered as a promising modality for better management of COVID-19-induced ALI/ARDS or coagulopathy.


Subject(s)
Acute Lung Injury/drug therapy , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Glycine/analogs & derivatives , Proteinase Inhibitory Proteins, Secretory/therapeutic use , Respiratory Distress Syndrome/drug therapy , Sulfonamides/therapeutic use , Acute Lung Injury/etiology , COVID-19/complications , Disseminated Intravascular Coagulation/etiology , Glycine/therapeutic use , Humans , Respiratory Distress Syndrome/etiology , Treatment Outcome
17.
Pharmacol Rep ; 72(6): 1446-1478, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-725461

ABSTRACT

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies.


Subject(s)
COVID-19/drug therapy , SARS-CoV-2/isolation & purification , Animals , COVID-19/virology , Clinical Trials as Topic , Humans
18.
Biochimie ; 177: 50-52, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-713261

ABSTRACT

Various interferon (IFN)-inducible transmembrane (IFITM) proteins are known to be expressed in human tissues though only IFITM 1-3 are inducible by IFN. Numerous studies have shown that activation of IFITM3 could suppress infection by influenza and coronaviruses such as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In view of the potential application of IFITM proteins' induction to target SARS-CoV-2 infection that causes COVID-19, this article layout insights into the known antiviral mechanisms and therapeutic agents related to IFITM. Blocking viral entry through various mechanisms and the potential application of the FDA approved immunosuppressant agent, mycophenolic acid, as inducer of IFITM3 are among those discussed.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Interferons/pharmacology , Membrane Proteins/drug effects , Mycophenolic Acid/pharmacology , Pneumonia, Viral/drug therapy , RNA-Binding Proteins/drug effects , Animals , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Humans , Immunosuppressive Agents/pharmacology , Membrane Proteins/immunology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , RNA-Binding Proteins/immunology , SARS-CoV-2
19.
Mini Rev Med Chem ; 20(18): 1900-1907, 2020.
Article in English | MEDLINE | ID: covidwho-706996

ABSTRACT

The global spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes COVID-19 has become a source of grave medical and socioeconomic concern to human society. Since its first appearance in the Wuhan region of China in December 2019, the most effective measures of managing the spread of SARS-CoV-2 infection have been social distancing and lockdown of human activity; the level of which has not been seen in our generations. Effective control of the viral infection and COVID-19 will ultimately depend on the development of either a vaccine or therapeutic agents. This article highlights the progresses made so far in these strategies by assessing key targets associated with the viral replication cycle. The key viral proteins and enzymes that could be targeted by new and repurposed drugs are discussed.


Subject(s)
COVID-19/therapy , Coronavirus 3C Proteases/antagonists & inhibitors , RNA Helicases/antagonists & inhibitors , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Antibodies/therapeutic use , Antiprotozoal Agents/therapeutic use , COVID-19/virology , Coronavirus 3C Proteases/metabolism , Humans , Nucleosides/analogs & derivatives , Nucleosides/metabolism , Nucleosides/therapeutic use , Protease Inhibitors/therapeutic use , RNA Helicases/metabolism , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology
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