Browsing by Author "Poduri, Ramarao"

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The Concept of Receptor and Molecule Interaction in Drug Discovery and Development
(Springer Singapore, 2021-02-18T00:00:00) Poduri, Ramarao; Jagadeesh, Gowraganahalli
The mechanisms by which drugs act are different and unique to each class as they involve interactions with pharmacological receptors, enzymes, ion channels, and cellular transport processes. Hormones, neurotransmitters, and autocoids are natural chemical messengers that have a role in physiological and pathological regulatory processes. The interpretation of their action is determined by the localization and functional capacity of the specific receptor with which the �first messenger� interacts and the concentration of the chemical to which the receptor is exposed. This chapter focuses on physiological receptors where many of the drugs act in a manner similar to endogenous agonists or interfere with their interaction at the target to alleviate the symptoms of a disease. While doing so, many of these molecules have shown selectivity for receptor subtypes and signaling pathways. This is based on pharmacological scales such as affinity and intrinsic efficacy, and methods to quantify them are described within a theoretical concept. Based on these two drug properties, the overt action of a drug may be agonism or antagonism. Added to this gallery are allosteric modulators (positive or negative), partial agonists, inverse agonists, and biased agonists and antagonists. These are discussed with examples. Such new drug development is believed to improve the treatment of diseases with fewer adverse effects as a drug�s therapeutic and adverse effects are mediated by distinct pathways. In this chapter, we have extended the classical concept of the initiation of a pharmacological response with the binding of a drug to a receptor to the complexity of selectivity for receptor subtypes and signaling pathways. � Springer Nature Singapore Pte Ltd. 2021.
Drug Discovery and Development: From Targets and Molecules to Medicines
(Springer Singapore, 2021-02-18T00:00:00) Poduri, Ramarao
This book describes the processes that are involved in the development of new drugs. The authors discuss the history, role of natural products and concept of receptor interactions with regard to the initial stages of drug discovery. In a single, highly readable volume, it outlines the basics of pharmacological screening, drug target identification, and genetics involved in early drug discovery. The final chapters introduce readers to stem therapeutics, pharmacokinetics, pharmacovigilance, and toxicological testing. Given its scope, the book will enable research scholars, professionals and young scientists to understand the key fundamentals of drug discovery, including stereochemistry, pharmacokinetics, clinical trials, statistics and toxicology. � Springer Nature Singapore Pte Ltd. 2021.
Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update
(Elsevier Ltd, 2021-03-18T00:00:00) Joshi, Gaurav; Thakur, Shikha; Mayank; Poduri, Ramarao
The review summarizes chloroquine (CQ) and its safer derivative hydroxychloroquine (HCQ) and its utility in Covid-19. Recently this well-established drug made its way back to the headlines during the SARS-CoV-2 pandemic. This led to an upsurge in the scientific arena with multiple research and review articles along with expert opinions and commentaries. The HCQ has received mixed judgements so far about its efficacy to be used in Covid-19 patients in a limited trial conducted all across the Globe. The purpose of our article is to put forth the history, pharmacodynamics, and pharmacokinetics, along with the existing studies favouring and disapproving the role of HCQ in the treatment of Covid-19. We grouped HCQ use at three stages, this includes HCQ for i. prophylactic use by asymptomatic health workers or peoples at higher risk; ii. patients having mild symptoms; iii. patients with extreme symptoms. The review critically discusses the underlying plausible reasons and mechanisms exploring HCQ in prophylactic management or treatment of SARS-CoV-2. Furthermore, we have critically analysed the reported pharmacokinetic parameters and compiled the proponent, opponent, or neutral opinions on the use of HCQ in Covid-19. Authors discretion is to conduct more studies considering the optimal dosing regimen and pharmacokinetics assessment. � 2021 Elsevier Ltd
Exploring the COVID-19 vaccine candidates against SARS-CoV-2 and its variants: where do we stand and where do we go?
(Taylor and Francis Ltd., 2021-12-03T00:00:00) Joshi, Gaurav; Borah, Pobitra; Thakur, Shweta; Sharma, Praveen; Mayank; Poduri, Ramarao
As of September 2021, 117 COVID-19 vaccines are in clinical development, and 194 are in preclinical development as per the World Health Organization (WHO) published draft landscape. Among the 117 vaccines undergoing clinical trials, the major platforms include protein subunit; RNA; inactivated virus; viral vector, among others. So far, USFDA recognized to approve the Pfizer-BioNTech (Comirnaty) COVID-19 vaccine for its full use in individuals of 16�years of age and older. Though the approved vaccines are being manufactured at a tremendous pace, the wealthiest countries have about 28% of total vaccines despite possessing only 10.8% of the total world population, suggesting an inequity of vaccine distribution. The review comprehensively summarizes the history of vaccines, mainly focusing on vaccines for SARS-CoV-2. The review also connects relevant topics, including measurement of vaccines efficacy against SARS-CoV-2 and its variants, associated challenges, and limitations, as hurdles in global vaccination are also kept forth. � 2021 Taylor & Francis Group, LLC.
Exploring the magic bullets to identify Achilles� heel in SARS-CoV-2: Delving deeper into the sea of possible therapeutic options in Covid-19 disease: An update
(Elsevier Ltd, 2020-11-27T00:00:00) Thakur, Shikha; Mayank; Sarkar, Bibekananda; Ansari, Arshad J.; Khandelwal, Akanksha; Arya, Anil; Poduri, Ramarao; Joshi, Gaurav
The symptoms associated with Covid-19 caused by SARS-CoV-2 in severe conditions can cause multiple organ failure and fatality via a plethora of mechanisms, and it is essential to discover the efficacious and safe drug. For this, a successful strategy is to inhibit in different stages of the SARS-CoV-2 life cycle and host cell reactions. The current review briefly put forth the summary of the SARS-CoV-2 pandemic and highlight the critical areas of understanding in genomics, proteomics, medicinal chemistry, and natural products derived drug discovery. The review further extends to briefly put forth the updates in the drug testing system, biologics, biophysics, and their advances concerning SARS-CoV-2. The salient features include information on SARS-CoV-2 morphology, genomic characterization, and pathophysiology along with important protein targets and how they influence the drug design and development against SARS-CoV-2 and a concerted and integrated approach to target these stages. The review also gives the status of drug design and discovery to identify the drugs acting on critical targets in SARS-CoV-2 and host reactions to treat Covid-19. � 2020 Elsevier Ltd
Historical Perspective of Drug Discovery and Development
(Springer Singapore, 2021-02-18T00:00:00) Poduri, Ramarao
Historically ever since the existence of humans on this planet the process of drug discovery was started by trial and error method. Initially they tested the natural products on self to understand the effects. Serendipity played a great role in the evolution of drug discovery. Isolation of active ingredients from plants started in the early nineteenth century. The advances in the field of chemical and biological sciences started the modern drug discovery and development. The regulatory processes became stringent due to some adverse events in the second half of the twentieth century. Currently the digital and disruptive technologies are changing the scenario of drug discovery and development and producing efficacious and safe drugs. � Springer Nature Singapore Pte Ltd. 2021.
Nanomedicine: Implications of Nanotoxicology
(Springer Singapore, 2021-02-18T00:00:00) Saifi, Mohd Aslam; Poduri, Ramarao; Godugu, Chandraiah
The expanding horizon of nanotechnology has covered most of the parts of our life including general household items to drug delivery and therapeutics. The progresses made in the nanotechnology field provided us some of the clinically useful nano-based products apart from the more than 50 products in pipeline. However, as these products are intended for human use, they also raise some critical safety concerns primarily due to their altered physicochemical properties different from the bulk. Further, the use of nanocarriers has also been found to be associated with different unwanted toxicological observations which depends on different factors. Hence, the safe and efficacious use of these nanocarriers strictly entails the comprehensive and thorough knowledge of the toxicological potential of nanocarriers. Further, the harmonious integration of academia, researcher, industries and regulatory bodies is warranted to ensure the proper regulation of their use. � Springer Nature Singapore Pte Ltd. 2021.
Pharmaceutical Industry, Academia, Regulatory Authorities and End User Collaboration in Successful Drug Discovery and Development
(Springer Singapore, 2021-02-18T00:00:00) Poduri, Ramarao
This chapter reviews the literature on the various factors (time-consuming processes, regulatory requirements, high attrition rate in phase III clinical trials and decrease in RandD productivity) contributed to increase the average cost of drug discovery. A better interaction between the stakeholders, i.e. pharmaceutical industry, academia, regulatory authorities and end users, results in efficacious, safe and affordable drugs to the benefit of the society. � Springer Nature Singapore Pte Ltd. 2021.
Recent efforts for drug identification from phytochemicals against SARS-CoV-2: Exploration of the chemical space to identify druggable leads
(Elsevier Ltd, 2021-04-03T00:00:00) Joshi, Gaurav; Sindhu, Jayant; Thakur, Shikha; Rana, Abhilash; Sharma, Geetika; Mayank; Poduri, Ramarao
Nature, which remains a central drug discovery pool, is always looked upon to find a putative druggable lead. The natural products and phytochemical derived from plants are essential during a global health crisis. This class represents one of the most practical and promising approaches to decrease pandemic's intensity owing to their therapeutic potential. The present manuscript is therefore kept forth to give the researchers updated information on undergoing research in allied areas of natural product-based drug discovery, particularly for Covid-19 disease. The study briefly shreds evidence from in vitro and in silico researches done so far to find a lead molecule against Covid-19. Following this, we exhaustively explored the concept of chemical space and molecular similarity parameters for the drug discovery about the lead(s) generated from in silico-based studies. The comparison was drawn using FDA-approved anti-infective agents during 2015�2020 using key descriptors to evaluate druglike properties. The outcomes of results were further corroborated using Molecular Dynamics studies which suggested the outcomes in alignment with chemical space ranking. In a nutshell, current research work aims to provide a holistic strategic approach to drug design, keeping in view the identified phytochemicals against Covid-19. � 2021 Elsevier Ltd
Selection of active antiviral compounds against COVID-19 disease targeting coronavirus endoribonuclease nendou/NSP15 via ligand-based virtual screening and molecular docking
(Bentham Science Publishers, 2020-12-15T00:00:00) Joshi, Gaurav; Poduri, Ramarao
Background: The rapid spread of SARS-CoV-2 has caused havoc and panic among individuals, which has further worsened due to the unavailability of a proven drug(s) regime. Objective: The current work involves drug repurposing from the pool of USFDA approved drugs involving in silico virtual screening technique against COVID-19. Materials and Methods: Methodology involves virtual screening of 8548 FDA approved drugs against target protein endoribonuclease NendoU (Nsp15) (PDB ID: 6VWW). Result: Virtual screening-based analysis enabled us to identify four drugs, Eprosartan, Inarigivir soproxil, Foretinib, and DB01813 that could plausibly target Nsp15 against COVID-19 disease. Conclusion: The work offers the scope to corroborate the findings via in vitro and in vivo techniques to identify the potential of selected leads against COVID-19. The outcome may also help in tracing their molecular mechanism(s) in addition to their development at the clinical level in the future. � 2021 Bentham Science Publishers.