Medicinal and Environmental Chemistry: Experimental Advances and Simulations (Part II)

Tahmeena Khan, Abdul Rahman Khan, Saman Raza, Tahmeena Khan, Abdul Rahman Khan, Saman Raza

• Publisher: Bentham Science Publishers
• Year: 2021
• Print ISBN: 9789814998321
• eBook ISBN: 9789814998307
• Topic: Physical Sciences
• Subtopic: Environmental Science

Medicinal and Environmental Chemistry: Experimental Advances and Simulations is a collection of topics that highlight the use of pharmaceutical chemistry to assess the environment or make drug design and chemical testing more environment friendly. The eleven chapters included in the second part of this book set cover diverse topics, blending the fields of environmental chemistry and medicinal chemistry and have been authored by experts, scientists and academicians from renowned institutions. This part is more specialized in nature, focusing primarily on the effects of air pollution and water contamination on human health. Chapters covering pharmaceutical interventions and pollution control measures, respectively follow these initial topics. Part II also features specialized topics that aim to address some unique challenges of the above mentioned problems including antibiotic pollution, pharmaceutical analysis of pollutants, chemosensors, biosteric modifications and new drug development strategies against SARS-CoV2. Key Features: 1. 11 topics which blend environmental chemistry and medicinal chemistry2. Contributions from more than 40 experts3. Includes topics covering effects of air pollution on human health and disease4. Includes specialized topics on pharmaceutical analysis in the environment, and modifications of compounds for pharmaceutical purposes5. Bibliographic references This reference is an essential source of information for readers and scholars involved in environmental chemistry, pollution management and pharmaceutical chemistry courses at graduate and undergraduate levels. Professionals and students involved in occupational medicine will also benefit from the wide range of topics covered.

Novel Drug Development Strategies- A Case Study With SARS-CoV-2

Iqbal Azad^{1, *}, Tahmeena Khan¹, Mohammad Irfan Azad², Abdul Rahman Khan¹

¹ Integral University, Lucknow, India

² Jamia Millia Islamia, New Delhi, India

Abstract

The current epidemic of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) has led to a major health crisis in 2020. SARS-CoV-2 has spike protein, polyproteins, nucleoproteins, and membrane proteins with RNA polymerase, 3-chymotrypsin-like protease, papain-like protease, helicase, glycoprotein, and accessory proteins. These are probable targets to be explored for the discovery of antiviral agents, still, to date, no definite treatment or vaccine has been discovered. Virtual screening with molecular docking has its advantage to speed up the drug development procedure in an accurate manner. In this chapter, novel computational strategies for drug discovery have been elaborated. Docking tools and drug filtering rules which may efficiently assist the drug development procedure and channelize the whole process in the right direction have also been discussed. A case study with 322 natural, semi-synthetic, and synthetic derivatives of citric acid (2-hydroxy-1,2,3-propane tricarboxylic acid), in search of a potential lead molecule to combat the novel coronavirus SARS-CoV-2, has been elaborated. The derivatives were explored from the PubChem database. The obtained library of compounds was filtered through Lipinski’s rules, out of which, 74 obeyed the rule and were further subjected to molecular docking investigation against the SARS-CoV-2 replicase polyprotein 1a or pp1a (ID: 6LU7), with AutoDock Vina and iGEMDOCK. Deptropine possessed the highest binding affinity, in terms of released binding energy (-7.4 kcal/mol), against the SARS-CoV-2 replicase polyprotein 1a.

Keywords: Citric acid, Computational strategies, Drug, Docking, Repurposing, SARS-CoV-2, Virtual screening.

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^* Corresponding author Iqbal Azad: Integral University, Lucknow, India; E-mail: [email protected]

INTRODUCTION

Three coronaviruses responsible for zoonotic diseases viz. Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), Middle East Respiratory Syndrome coronavirus (MERS-CoV),and SARS-CoV-2, have caused lethal

pneumonia in humans by crossing the species barrier in recent times [1]. In 2002, SARS-CoV originated in the Guangdong region of China and was transmitted through the air to adjacent regions, leading to approximately 8,098 infections and 774 deaths [2, 3]. MERS-CoV outbreak took place in 2012 in the Arabian Peninsula and became a major public health issue. MERS-CoV reached 27 countries, infecting ~2,494 people and causing 858 casualties [4]. In December 2019, in Wuhan, a novel coronavirus (SARS-CoV-2) was discovered, spreading all over the world within few months [5]. It is linked with lethal pneumonia infecting over one crore people worldwide and causing more than five lakh deaths, till 13^th July 2020 (Table 1). MERS-CoV was found to be originated from bats [6]; similarly, SARS-CoV and SARS-CoV-2 which are closely associated, also originated from bats. SARS-CoV-2 is a positive-sense ssRNA virus. It is a β-coronavirus like MERS-CoV and SARS-CoV. The initial viral 30 kb RNA genome is termed as an open reading frame (ORF1a/b) part and interpreted through polyproteins (pp1a and pp1ab). The remaining portion of the viral RNA genome encrypts accessory proteins as well as four important structural proteins, namely spike (S) glycoprotein, small envelope (E) protein, matrix (M) protein, and nucleocapsid (N) protein [7].

Factors affecting the spread of SARS-CoV-2

Environmental Factors

SARS-CoV-2 is a positive-sense ssRNA virus that mainly causes respiratory failure [8]. In the spread of the virus, numerous factors are involved, associated with the environment and the human correlation [9], in which migration, community interactions, dispersal of the human population, agricultural development, climate transformation as well as interaction with animals find a prominent place [10]. The correlation between the viral spread with major environmental factors like humidity, ambient temperature, and wind speed, etc. has not been satisfactorily explored. How the virus crosses the nose, ears, eyes, and mouth, etc. is not well recognized, and the release of SARS-CoV-2 as droplets and aerosols have also not being investigated thoroughly [11]. Owing to the versatility and mutation of COVID-19, control and prevention have drawn serious and urgent concern [12].

Concerns have originated to establish a clear relationship between environmental factors and SARS-CoV-2 cases [13]. According to the World Health Organization (WHO) (2020), sunlight, pH variations, and high temperature may curb viral growth [14]. A study conducted in China and Italy described the association between the SARS-CoV-2 spread with several environmental factors, such as humidity, wind speed, and temperature [15, 16]. Some researchers have described the resistance of the SARS-CoV-2 at low and high temperatures and found that at 4 °C its survival is for a longer period, whereas at 70 °C the virus survived only for 5 minutes. Wang et al. in their study conducted in 26 areas in China with a sample size of 24,139 positive SARS-CoV-2 cases, showed that a 1 °C rise in the minimum ambient air temperature decreased the cases by 0.86% [16, 17].

Table 1 Total cases of SARS-CoV-2 in top 10 countries (https://news.google.com/covid19) till 13^th July 2020.

S. No.	Country	Confirmed Cases	Recovered Cases	Deaths
1	United States	33,66,515	9,88,656	5,71,444
2	Brazil	18,66,176	12,13,512	1,37,191
3	India	8,78,254	5,53,470	72,151
4	Russia	7,33,699	5,04,021	23,174
5	Peru	3,26,326	2,42,474	11,439
6	Chile	3,15,041	2,83,902	11,870
7	Mexico	2,99,750	1,84,764	6,979
8	United Kingdom	2,90,133	No data	35,006
9	South Africa	2,76,242	1,34,874	44,830
10	Iran	2,59,652	No data	4,079
11	Worldwide	1,29,45,505	70,01,675	5...

Table of contents

• Welcome
• Table of Content
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• FOREWORD
• PREFACE
• List of Contributors
• Air Pollution and its Impact on Respiratory Health
• Cytochrome P450 and Health Hazards of Smog
• Pharmaceutical and Modelling Interventions for Environmental Pollution Related Chronic Obstructive Pulmonary Disease
• Arsenic Toxicity of Groundwater and Its Remediation for Drinking Water
• Studies on Polymeric Ceramic Composite Membranes for Water Treatment
• Chemosensors For Anions Of Biological and Environmental Relevance
• Antibiotic Pollution: Challenges and Strategies
• Analytical Advancement for Pharmaceuticals Quantification in Environmental Matrices
• Use of Bioisosteric Functional Group Replacements or Modifications for Improved Environmental Health
• Gold and Silver Nanoparticle Synthesis by Pyrus and Eurya: Environment-Friendly Therapeutic Agents
• Novel Drug Development Strategies- A Case Study With SARS-CoV-2