Editorial Current Molecular Pharmacology, 2022, Vol. 15, No.

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EDITORIAL

Molecular Insights into Agonist/Antagonist Effects on Macromolecules Involved in

Human Disease Mechanisms

Biological macromolecules, such as proteins, lipids, carbohydrates, and nucleic acids, play a major role in the proper func-
tioning of the human organism. When these macromolecules are unable to function effectively, the body's system malfunc-
tions, and it is called a disease by the medical community. The structure-function relationships between these macromole-
cules are essential for understanding normal and pathological conditions, as well as the binding influence of agonist and an-
tagonist molecules. One of the greatest medical discoveries is the discovery of medicines, significantly impacting human
health. Non-communicable and communicable diseases pose an enormous threat to economic and social development for
centuries to come due to their rapid spread. The current COVID-19 pandemic, caused by the devastating Severe Acute Res-
piratory Syndrome Coronavirus 2, is an example. The pharmaceutical sector has to face a huge challenge in terms of develop-
ing drugs to treat and manage chronic diseases. Research on therapeutic chemicals from natural sources with high medicinal
potential has been of considerable interest, but its success is still modest. A new generation of biotechnological and synthetic
biology technologies must be employed to identify novel targets for treatment. In their study, Kumar et al. has explored the
inactivation of parathyroid hormone, focusing on the discovery of drugs for hyperparathyroidism [1]. Human physiology is
regulated by the precise coordination of hormones. The endocrine system's parathyroid hormone (PTH) controls the calcium
and phosphate levels in the human body. Hyperparathyroidism and hypoparathyroidism may occur in non-physiological situ-
ations caused by external or internal sources. Calcium deposition occurs in hyperparathyroidism because elevated PTH
stimulates cell receptors in the bones, kidneys, and intestines. Eventually, it develops a variety of symptoms, including kid-
ney stones. However, as of now, the drug that directly inhibits PTH's activity is currently unavailable. Therefore, it is of great
value to develop novel small molecules or any other means of modulating the PTH function. According to Kumar and col-
leagues, hyperparathyroidism can be treated with small molecules or other methods which influence the N-terminus of PTH.
The article by Girija et al. has explored the family of polyketide and non-ribosomal peptides for drug development [2]. There
are two types of enzymes, known as polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS), that pro-
duce these peptides, which can be found in both microorganisms and plants. Due to their simple structure, catalytic capabil-
ity, and diversity, these enzymes have great potential in medicine. As discussed by Girija et al., future bioprospecting and
drug discovery will benefit from polyketides and non-ribosomal peptides, as well as techniques to optimize the development
of their derivatives and scaffolds. Sikdar et al. has reviewed the antivirals for curing human diseases by exploring the history
of antiviral compounds and how the methods have changed from past to present. Different auxiliary science strategies are
described that can serve as a referral for therapeutic innovation [3]. Precilla et al. explored the Wnt/β-catenin antagonists,
especially for glioblastoma multiforme (GBM), through computational tools to find out the novel combinations against the
Wnt/β-catenin signalling pathway [4]. Precilla et al. claimed that their study is the first of its kind to define the combined
interactions of these medications with the Wnt/-catenin signalling in silico, which they believe will open new paths for com-
bination therapy in GBM treatment. Durairajan et al. evaluated the efficacy of medicinal plant-derived compounds in alleviat-
ing tau-mediated neurodegeneration [5]. Amyloid-beta (Aβ) plaques and hyperphosphorylated tau-associated neurofibrillary
tangles are two features of Alzheimer's disease that can be observed in the brains of patients. Aβ targeted therapeutic drugs
have indicated that alternative targets, such as tau, should be studied to discover more effective and safer drugs. Plant-derived
chemicals capable of regulating the tau protein, which is increased and hyperphosphorylated in Alzheimer's disease (AD), are
the focus of the study. Furthermore, Durairajan and colleagues have explored the compounds, including indolines, phenolics,
flavonoids, coumarins, alkaloids, and iridoids, which have been scientifically proven to be tau-targeting candidates for the
treatment of AD. Sindhu et al. analysed the cytochrome bc1-aa3 oxidase super complex as drug targets for tuberculosis by
reporting the mechanism of the enzyme at the atomic level [6]. Cytochrome bc1-aa3 super complex from Mycobacterium
tuberculosis is a prominent target for antibiotic activity. Mycobacterial cytochrome bc1-aa3 super complex with open and
closed conformations has recently been resolved by cryo-EM, paving new ways for studying its structure and function to de-
sign more effective, innovative therapies for pulmonary tuberculosis treatment. Bhavaniramya et al. performed a comprehen-
sive analysis of SARS-CoV-2 drug targets and explored the medications against the novel coronavirus [7]. They discussed
the multiple proteins encoded in the genome, many of which have no known functions, yet share a remarkable degree of se-
quence identity with other proteins. Numerous trials are currently underway to study the potential therapeutic medicines for

1874-4672/22 © 2022 Bentham Science Publishers

2 Current Molecular Pharmacology, 2022, Vol. 15, No. 2 Editorial

viral infections. Selvaraj et al., has performed the deep structural studies on SARS-CoV-2 proteins, by focusing on the active
site morphology towards structure-based drug design [8]. Targeting coronaviral proteins that are involved in host cell entry,
replicating and invading host cells are potential therapeutic strategies. Even though remdesivir and other repurposed medica-
tions are used in emergencies, there is still no approved treatment for COVID-19. A review of the molecular life cycle of
SARS-CoV-2 was performed by Selvaraj et al. to summarize possible drug targets, structural insights and active site contour
map analyses of those selected SARS-CoV-2 protein targets for drug discovery, and immunology and pathophysiology of the
disease. We hope multidisciplinary topics discussed along with the theme issue will promote further discussion between the
researchers and macromolecular biologist involved in exploring human disease mechanisms. As the guest editors, we would
like to thank all the authors and co-authors for their excellent contributions. In addition, we would like to thank scientific
experts who provided their strong comments and suggestions as reviewers to improve the quality of this special issue. Final-
ly, we would like to express our sincere appreciation to Prof. Michael Kahn, the editor-in-chief, editorial manager Humaira
Shabbir, copy editors, and all the editorial staff of the Current Molecular Pharmacology, Bentham Science Publishers, for
providing excellent opportunity and experience while working on this thematic issue.

REFERENCES

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Dr. Chandrabose Selvaraj Dr. Sugunadevi Sakkiah Dr. Dhurvas Chandrasekaran Dinesh
Senior Researcher Research Scientist, Post-Doctoral Fellow
Computer-Aided Drug Design and Molecu- C4 Therapeutics, Watertown MA, Institute of Organic Chemistry and
lar Modelling Lab, U.S.A Biochemistry of the CAS,
Department of Bioinformatics, Email: suguna.dv@gmail.com Prague,
Alagappa University Czechia
Karaikudi, Tamil Nadu, India Email: dinesh@uochb.cas.cz
Email: selnikraj@bioclues.org