Phosphodiesterases as Drug Targets in Selected Respiratory Diseases

: Corona viruses are enveloped, single-stranded RNA (Ribonucleic acid) viruses and they cause pandemic diseases having a devastating effect on both human healthcare and the global economy. To date, six corona viruses have been identified as pathogenic organisms which are significantly responsible for the infection and also cause severe respiratory diseases. Among them, the novel SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) caused a major outbreak of corona virus diseases 2019 (COVID-19). Coronaviridae family members can affects both humans and animals. In human, corona viruses cause severe acute respiratory syndrome with mild to severe outcomes. Several structural and genomics have been investigated, and the genome encodes about 28 proteins most of them with unknown function though it shares remarkable sequence identity with other proteins. There is no potent and licensed vaccine against SARS-CoV-2 and several trials are underway to investigate the possible therapeutic agents against viral infection. However, some of the antiviral drugs that have been investigated against SARS-CoV-2 are under clinical trials. In the current review we comparatively emphasize the emergence and pathogenicity of the SARS-CoV-2 and their infection and discuss the various putative drug targets of both viral and host receptors for developing effective vaccines and therapeutic combinations to overcome the viral outbreak.

Download Full-text

Discovery of Anti-2019-nCoV Agents from 38 Chinese Patent Drugs toward Respiratory Diseases via Docking Screening

10.20944/preprints202002.0254.v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Yong-Ming Yan ◽

Xin Shen ◽

Yong-Kai Cao ◽

Jiao-Jiao Zhang ◽

Yan Wang ◽

...

Keyword(s):

Chlorogenic Acid ◽

Drug Targets ◽

Respiratory Diseases ◽

Drug Repurposing ◽

Botanical Knowledge ◽

Main Protease ◽

Common Strategy ◽

Chinese Patent ◽

Novel Coronavirus ◽

Approved Drugs

The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.

Download Full-text

Potassium channels as drug targets for therapeutic intervention in respiratory diseases

Expert Opinion on Therapeutic Patents ◽

10.1517/13543770802553798 ◽

2008 ◽

Vol 18 (12) ◽

pp. 1361-1384 ◽

Cited By ~ 5

Author(s):

Antonio Nardi ◽

Joachim Demnitz ◽

Maria L Garcia ◽

Riccardo Polosa

Keyword(s):

Potassium Channels ◽

Therapeutic Intervention ◽

Drug Targets ◽

Respiratory Diseases

Download Full-text

Gut microbiome a promising target for management of respiratory diseases

Biochemical Journal ◽

10.1042/bcj20200426 ◽

2020 ◽

Vol 477 (14) ◽

pp. 2679-2696

Author(s):

Riddhi Trivedi ◽

Kalyani Barve

Keyword(s):

Respiratory Diseases ◽

New Technology ◽

Bacterial Flora ◽

Systemic Circulation ◽

The Body ◽

Lung Pathology ◽

Promising Target ◽

Current Therapies ◽

Intestinal Microbial Flora ◽

On Chip

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut–lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut–lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.

Download Full-text