Multidrug resistance crisis during COVID-19 pandemic: Role of anti-microbial peptides as next-generation therapeutics

Abstract

The decreasing effectiveness of conventional drugs due to multidrug-resistance is a major challenge for the scientific community, necessitating development of novel antimicrobial agents. In the present era of coronavirus 2 (COVID-19) pandemic, patients are being widely exposed to antimicrobial drugs and hence the problem of multidrug-resistance shall be aggravated in the days to come. Consequently, revisiting the phenomena of multidrug resistance leading to formulation of effective antimicrobial agents is the need of the hour. As a result, this review sheds light on the looming crisis of multidrug resistance in wake of the COVID-19 pandemic. It highlights the problem, significance and approaches for tackling microbial resistance with special emphasis on anti-microbial peptides as next-generation therapeutics against multidrug resistance associated diseases. Antimicrobial peptides exhibit exceptional mechanism of action enabling rapid killing of microbes at low concentration, antibiofilm activity, immunomodulatory properties along with a low tendency for resistance development providing them an edge over conventional antibiotics. The review is unique as it discusses the mode of action, pharmacodynamic properties and application of antimicrobial peptides in areas ranging from therapeutics to agriculture.

Rhodococcus strains as a good biotool for neutralizing pharmaceutical pollutants and obtaining therapeutically valuable products: Through the past into the future

“…On the other hand, the synthesis of antimicrobial agents inhibits the growth of certain microorganisms, including pathogenic bacteria. Against the background of antibiotic and multidrug resistance, this property of rhodococci is of great interest to the pharmaceutical industry and is a powerful impetus to the development and discovery of alternative antimicrobial molecules ( Sharma et al, 2022 ; Figure 7 ).…”

Smart therapies against global pandemics: A potential of short peptides

“…Antimicrobial peptides (AMPs), especially host defense peptides, are first-line pan-agents to combat resistant multi-drug microorganisms, revealing their immense potential and multifaceted nature. AMPs exhibit a unique mechanism of action based on rapid microbes killing at low concentration with immunomodulatory ability and low susceptibility to resistance ( Sharma et al, 2022 ). Interestingly, many AMPs reveal antiviral activity too ( Lee et al, 2022 ).…”

“…Antiviral and antifungal mechanisms of AMP action are described elsewhere ( Vanzolini et al, 2022 ). Short and modified AMPs have better therapeutic efficacy, reduced cytotoxicity, decreased proteolytic digestion, cheaper production on large scale ( Sharma et al, 2022 ). These new deep-learning based tools are useful for fast and cost-effective prediction of suitable AMPs ( Li et al, 2022 ).…”

Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2

“…Thus, new technologies/strategies for the rapid development of therapeutics of novel protein pathogens targets are needed for an effective response to future pandemics ( Pardi and Weissman, 2020 ). Among the two emerging promiscuous approaches, which may significantly reduce the time to develop new treatments in case of novel pathogens, are the drug repurposing approach ( Pushpakom et al, 2019 ) and peptide-based therapeutics mainly targeting protein-protein interactions ( Shah et al, 2022 ; Sharma et al, 2022 ).…”

“…The protein-protein recognition process between the receptor-binding domain (RBD) of the virus’ spike (S) glycoprotein and human receptor angiotensin-converting enzyme 2 (ACE2) is involved in the early stages of the SARS-CoV-2 life cycle leading to the host cell membrane fusion and finally the virus replication ( Walls et al, 2020 ). Immediately after the outbreak of SARS-CoV-2, the endeavor to develop a new targeted therapy against novel coronavirus was started, and one of the extensively explored drug targets in the scientific literature is the mentioned virus-host protein-protein interaction ( Ghosh and Weinberg, 2021 ; Shah et al, 2022 ; Sharma et al, 2022 ). Many peptides with similar properties were proposed by other groups using different strategies based on natural or synthetic peptide libraries or even similar to our approach based on different, native parts of h ACE2 ( Baig et al, 2020 ; Barh et al, 2020 ; Chatterjee et al, 2020 ; Chaturvedi et al, 2020 ; Han and Král, 2020 ; Huang et al, 2020 ; Jaiswal and Kumar, 2020 ; Sitthiyotha and Chunsrivirot, 2020 ; Zhao et al, 2022 ).…”