Discovery of Antivirals Using Phage Display

Abstract

The latest coronavirus disease outbreak, COVID-19, has brought attention to viral infections which have posed serious health threats to humankind throughout history. The rapid global spread of COVID-19 is attributed to the increased human mobility of today’s world, yet the threat of viral infections to global public health is expected to increase continuously in part due to increasing human–animal interface. Development of antiviral agents is crucial to combat both existing and novel viral infections. Recently, there is a growing interest in peptide/protein-based drug molecules. Antibodies are becoming especially predominant in the drug market. Indeed, in a remarkably short period, four antibody therapeutics were authorized for emergency use in COVID-19 treatment in the US, Russia, and India as of November 2020. Phage display has been one of the most widely used screening methods for peptide/antibody drug discovery. Several phage display-derived biologics are already in the market, and the expiration of intellectual property rights of phage-display antibody discovery platforms suggests an increment in antibody drugs in the near future. This review summarizes the most common phage display libraries used in antiviral discovery, highlights the approaches employed to enhance the antiviral potency of selected peptides/antibody fragments, and finally provides a discussion about the present status of the developed antivirals in clinic.

Receptor-binding domain-anchored peptides block binding of severe acute respiratory syndrome coronavirus 2 spike proteins with cell surface angiotensin-converting enzyme 2

“…Frontiers in Microbiology 06 frontiersin.org pathogen invasions in this lab (Zhao et al, 2012) or others (Hall et al, 2009;Wei et al, 2020). This study and several other efforts (Anand et al, 2021;Sokullu et al, 2021;Ballmann et al, 2022;Labriola et al, 2022;Petrenko et al, 2022;Sevenich et al, 2022;Yang et al, 2022) demonstrated that PhD was a plausible method for generating possible therapeutics to treat COVID-19 as well. For example, Petrenko used phage-displayed spike S1 protein mimotopes to search for "all" cellular receptors, including authentic and alternative ones.…”

Preparation of a Nanobody Specific to Dectin 1 and Its Anti-inflammatory Effects on Fungal Keratitis

“…Phage display is a feasible method for selection of a particular domain of an antigen. 41,42 Through the construction of a large-capacity natural nanobody-gene library, a variety of nanobodies can be prepared without…”

Protein Engineering: Advances in Phage Display for Basic Science and Medical Research

“…The resulting immune library does not need to be as large as naïve libraries, since the immunized pool of lymphocytes would contain multiple proliferated B-cell clones targeting the antigen. Some naïve antibody libraries represent 10 11 individual clones or more [ 18 , 21 , 22 ], reaching practical limit of the phage antibody library size preset around 10 12 value, due to the technical limitation of bacterial transformation, culturing, and storage [ 62 ]. While theoretical diversity of the naïve combinatorial libraries is much higher than their achievable size, there is significantly less variety of the naturally paired VH-VLs in the mammalian immune system.…”

“…Since Smith and Winter published their pivotal studies in 1980s-1990s [ 9 - 14 ], the scope and capabilities of phage display have been enormously expanded [ 15 - 20 ]. Construction of large numbers of phage display peptide and antibody libraries containing 10 11-12 unique members have been achieved [ 18 , 21 , 22 ] and are commercially available (New England BioLabs, MoBiTec GmbH, and Creative Biolabs, Shirley, NY, USA)…”