Citation: Bakare, O.O.; Gokul, A.; Keyster, M. Analytical Studies of Antimicrobial Peptides as Diagnostic Biomarkers for the Detection of Bacterial and Viral Pneumonia. Bioengineering 2022, 9, 305. https:// doi.org/10.3390/bioengineering9070305 Academic Editors: Giuseppe Cesarelli, Carlo Ricciardi, Leandro Donisi and Alfonso Maria Ponsiglione Received: 24 May 2022 Accepted: 29 June 2022 Published: 11 July 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). bioengineering Article Analytical Studies of Antimicrobial Peptides as Diagnostic Biomarkers for the Detection of Bacterial and Viral Pneumonia Olalekan Olanrewaju Bakare 1,2, * , Arun Gokul 1,3 and Marshall Keyster 1 1 Environmental Biotechnology Laboratory (EBL), Department of Biotechnology, University of the Western Cape, Cape Town 7535, South Africa; agokul5@gmail.com (A.G.); mkeyster@uwc.ac.za (M.K.) 2 Department of Biochemistry, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Sagamu 120107, Ogun State, Nigeria 3 Department of Plant Sciences, Qwaqwa Campus, University of the Free State, Phuthadithjaba 9866, South Africa * Correspondence: lekanbakare77@gmail.com; Tel.: +27-603112776 Abstract: Pneumonia remains one of the leading causes of infectious mortality and significant economic losses among our growing population. The lack of specific biomarkers for correct and timely diagnosis to detect patients’ status is a bane towards initiating a proper treatment plan for the disease; thus, current biomarkers cannot distinguish between pneumonia and other associated conditions such as atherosclerotic plaques and human immunodeficiency virus (HIV). Antimicrobial peptides (AMPs) are potential candidates for detecting numerous illnesses due to their compensatory roles as theranostic molecules. This research sought to generate specific data for parental AMPs to identify viral and bacterial pneumonia pathogens using in silico technology. The parental antimicrobial peptides (AMPs) used in this work were AMPs discovered in our previous in silico analyses using the HMMER algorithm, which were used to generate derivative (mutated) AMPs that would bind with greater affinity, in order to detect the bacterial and viral receptors using an in silico site-directed mutagenesis approach. These AMPs’ 3D structures were subsequently predicted and docked against receptor proteins. The result shows putative AMPs with the potential capacity to detect pneumonia caused by these pathogens through their binding precision with high sensitivity, accuracy, and specificity for possible use in point-of-care diagnosis. These peptides’ tendency to detect receptor proteins of viral and bacterial pneumonia with precision justifies their use for differential diagnostics, in an attempt to reduce the problems of indiscriminate overuse, toxicity due to the wrong prescription, bacterial resistance, and the scarcity and high cost of existing pneumonia antibiotics. Keywords: antimicrobial peptides; bacteria; viruses; databases; machine learning tool; diagnostics; receptors 1. Introduction Pneumonia is challenging because of its significant impact on global health [1]. It is characterized by specific infections with a distinct clinical source, presentation, epidemi- ology, and pathogenesis [2]. The disease arises from an infection in the lower respiratory tract, starting with inflammation and impaired tissue functioning [3]. Diagnosis of the disease may be difficult for an established respiratory condition, cardiac failure, and non-pneumonic respiratory infection because there is no evidence-based consensus on its clinical signs and predictive symptoms [4]. The diagnostic biomarkers used at present are produced in response to other conditions such as HIV and atherosclerosis [5]. The use of antibodies has remained questionable despite its high sensitivity due to challenges such as cross-reactivity [6]. The discovery of more specific and sensitive biomarkers for detecting pneumonia in patients’ samples is an ultimate goal of researchers to reduce the high mortality arising from the disease. Bioengineering 2022, 9, 305. https://doi.org/10.3390/bioengineering9070305 https://www.mdpi.com/journal/bioengineering