Alpha-1 Antitrypsin for COVID-19 Treatment: Dual Role in Antiviral Infection and Anti-Inflammation

Many drugs have been approved for clinical trials for the treatment of COVID-19 disease, focusing on either antiviral or anti-inflammatory approaches. Combining antiviral and anti-inflammatory drugs or therapies together may be more effective. Human alpha-1 antitrypsin (A1AT) is a blood circulating glycoprotein that is best known as a protease inhibitor. It has been used to treat emphysema patients with A1AT deficiency for decades. We and others have demonstrated its role in reducing acute lung injury by inhibiting inflammation, cell death, coagulation, and neutrophil elastase activation. Recently, A1AT has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by inhibiting transmembrane serine protease 2 (TMPRSS2), a protease involved in the entry of SARS-CoV-2 into host cells. This dual role of both antiviral infection and anti-inflammation makes A1AT a unique and excellent candidate for COVID-19 treatment. Three clinical trials of A1AT for COVID-19 treatment have recently been approved in several countries. It is important to determine whether A1AT can prevent the progress from moderate to severe lung injury and eventually to be used to treat COVID-19 patients with acute respiratory distress syndrome.

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Pharmacotherapy of Juvenile Idiopathic Arthritis

Journal of Pharmacy Practice ◽

10.1177/0897190008322245 ◽

2008 ◽

Vol 22 (1) ◽

pp. 17-28 ◽

Cited By ~ 1

Author(s):

Edward A. Bell

Keyword(s):

Clinical Trials ◽

Juvenile Idiopathic Arthritis ◽

Initial Therapy ◽

Biologic Agents ◽

Rheumatic Disorder ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Therapy Methotrexate

Juvenile idiopathic arthritis is the most common rheumatic disorder of childhood, and is defined as arthritis beginning prior to the age of 16 years, lasting more than 6 weeks, with an unknown cause. Seven subtypes of juvenile idiopathic arthritis have recently been categorized and named. These subtypes differ broadly in the number of affected joints and the presence of systemic illness. Although many children with juvenile idiopathic arthritis may achieve remission prior to entering adulthood, many others will continue to have debilitating disease into adulthood. Pharmacotherapy plays a major role in the treatment of juvenile idiopathic arthritis. Nonsteroidal anti-inflammatory drugs and corticosteroids can be beneficial for many children and are used as initial therapy. Methotrexate may offer benefits to children unresponsive to these initial agents. Studies evaluating the use of several biologic agents and immunosuppressants have recently been published, and the role of these drugs for children with juvenile idiopathic arthritis is being assessed. Major clinical trials and pediatric implications are reviewed.

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Clinical pharmacological particular qualities of original ibuprofen different forms in treatment of diseases manifesting by pain

Consilium Medicum ◽

10.26442/20751753.2021.2.200727 ◽

2021 ◽

Vol 23 (2) ◽

pp. 175-180

Author(s):

Mikhail V. Pchelintsev ◽

Keyword(s):

Clinical Trials ◽

Present Article ◽

Randomized Clinical Trials ◽

Analgesic Efficacy ◽

Special Consideration ◽

Nociceptive Pain ◽

Efficacy And Safety ◽

Inflammatory Drugs ◽

Anti Inflammatory

In the present article, the role of non-steroidal anti-inflammatory drugs in treatment of different diseases manifesting by nociceptive pain is viewed. Special consideration is given to Ibuprofen, which is very often used as a non-prescription analgesic and/or anti-pyretic agent. Using the examples of randomized clinical trials and meta-analyzes carried on their basis, a high comparative analgesic efficacy and safety of use of original ibuprofen, Nurofen®, in different pharmaceutical forms in particular in a form of rapidly absorbed tablets and in combination with paracetamol.

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Role of Camphlobacter pylori and non steroidal anti-inflammatory drugs in the pathogenesis of peptic ulcer and pharmacological approaches for the treatment of peptic ulcer disease

Gastroenterology & Hepatology Open Access ◽

10.15406/ghoa.2019.10.00352 ◽

2019 ◽

Vol 10 (1) ◽

Author(s):

Amrish Kumar ◽

Mansi Verma ◽

Vipin Kumar Garg ◽

Avnesh Kumar ◽

Anjana Sharma ◽

...

Keyword(s):

Peptic Ulcer ◽

Peptic Ulcer Disease ◽

Ulcer Disease ◽

Inflammatory Drugs ◽

Anti Inflammatory

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The Efficacy of Anti-inflammatory Agents in the Prevention of Atrial Fibrillation Recurrences

Current Medicinal Chemistry ◽

10.2174/1389450121666200302095103 ◽

2020 ◽

Vol 28 (1) ◽

pp. 137-151

Author(s):

Homa Nomani ◽

Sara Saei ◽

Thomas P. Johnston ◽

Amirhossein Sahebkar ◽

Amir Hooshang Mohammadpour

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Therapeutic Option ◽

General Rule ◽

Promising Candidate ◽

Term Basis ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Meta Analyses ◽

Af Recurrence

: Several studies have indicated an association between inflammation and the recurrence of Atrial Fibrillation (AF), especially after ablation, which is a therapeutic option leading to local inflammation. On the other hand, each AF can lead to another AF, as a general rule. Thus, preventing recurrences of AF is extremely important for patient outcomes. In this paper, we attempted to review the effect of medicinal agents with anti-inflammatory properties on the prevention of AF recurrence. There are several randomized controlled trials (RCTs) and meta-analyses on the prevention of AF recurrence using agents with anti-inflammatory properties, which include steroids, colchicine, statins, and n-3 fatty acids (n-3 FA). Clinical trials evaluating the efficacy of anti-inflammatory drugs in preventing the recurrence of AF led to inconsistent results for corticosteroids, statins and n-3 FAs. These results may be related to the fact that inflammation is not the only factor responsible for triggering recurrences of AF. For example, the presence of structural, mechanical and electrical remodeling could potentially be the most important factors that trigger recurrences of AF but these factors have not been addressed in most of the reported studies. Therefore, future clinical trials are needed to compare the efficacy of anti-inflammatory drugs in AF patients with, or without other factors. For colchicine, a potent anti-inflammatory drug, there are limited studies. However, all the studies investigating colchicine in the context of AF were consistent and promising, especially when colchicine was used on a short-term basis following ablation in patients with paroxysmal AF. Therefore, colchicine could be a promising candidate for further clinical studies involving recurrent AF.

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The Role of Anti-Inflammatory Drugs in Respiratory Diseases - Pirfenidone, Penicillamine, Chloroquine and Chlorambucil

Current Respiratory Medicine Reviews ◽

10.2174/1573398x10666140526234959 ◽

2014 ◽

Vol 9 (5) ◽

pp. 334-343

Author(s):

Benjamin Courchia ◽

Aya Gozlan ◽

Maor Waldman ◽

Or Kalchiem-Dekel

Keyword(s):

Respiratory Diseases ◽

Inflammatory Drugs ◽

Anti Inflammatory

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Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

Pharmaceuticals ◽

10.3390/ph14070692 ◽

2021 ◽

Vol 14 (7) ◽

pp. 692

Author(s):

Ryldene Marques Duarte da Cruz ◽

Francisco Jaime Bezerra Mendonça-Junior ◽

Natália Barbosa de Mélo ◽

Luciana Scotti ◽

Rodrigo Santos Aquino de Araújo ◽

...

Keyword(s):

Inflammatory Diseases ◽

Structural Characteristics ◽

Tiaprofenic Acid ◽

Inflammatory Activity ◽

Drug Candidates ◽

Biological Target ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Privileged Structures

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

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Macrophage Activation and Cytokine Release Syndrome in COVID-19: Current Updates and Analysis of Repurposed and Investigational Anti-Cytokine Drugs

Drug Research ◽

10.1055/a-1291-7692 ◽

2021 ◽

Cited By ~ 1

Author(s):

Ashif Iqubal ◽

Farazul Hoda ◽

Abul Kalam Najmi ◽

Syed Ehtaishamul Haque

Keyword(s):

Immune Response ◽

Clinical Trials ◽

Macrophage Activation ◽

Fatality Rate ◽

Cytokine Storm ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Disease Condition ◽

Inflammatory Drugs ◽

Anti Inflammatory

AbstractCoronavirus disease (COVID-19) emerged from Wuhan, has now become pandemic and the mortality rate is growing exponentially. Clinical complication and fatality rate is much higher for patients having co-morbid issues. Compromised immune response and hyper inflammation is hall mark of pathogenesis and major cause of mortality. Cytokine release syndrome (CRS) or cytokine storm is a term used to affiliate the situation of hyper inflammation and therefore use of anti-cytokine and anti-inflammatory drugs is used to take care of this situation. Looking into the clinical benefit of these anti-inflammatory drugs, many of them enter into clinical trials. However, understanding the immunopathology of COVID-19 is important otherwise, indiscriminate use of these drugs could be fetal as there exists a very fine line of difference between viral clearing cytokines and inflammatory cytokines. If any drug suppresses the viral clearing cytokines, it will worsen the situation and hence, the use of these drugs must be based on the clinical condition, viral load, co-existing disease condition and severity of the infection.

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