Biosimilars Targeting Pathogens: A Comprehensive Review of Their Role in Bacterial, Fungal, Parasitic, and Viral Infections

Abstract

Biosimilars represent medicinal products that exhibit a high degree of similarity to an already sanctioned reference biologic agent, with negligible clinically significant disparities concerning safety, purity, or potency. These therapeutic modalities are formulated as economically viable substitutes for established biologics, thereby facilitating increased accessibility to sophisticated treatments for a range of medical conditions, including infectious diseases caused by bacterial, fungal, and viral pathogens. The current landscape of biosimilars includes therapeutic proteins, such as monoclonal antibodies, antimicrobial peptides, antiviral peptides, and antifungal peptides. Here, we discuss the obstacles inherent in the development of biosimilars, including the rapid mutation rates of pathogens. Furthermore, we discuss innovative technologies within the domain, including antibody engineering, synthetic biology, and cell-free protein synthesis, which exhibit potential for improving the potency and production efficiency of biosimilars. We end with a prospective outlook to highlight the importance and capacity of biosimilars to tackle emerging infectious diseases, highlighting the imperative need for ongoing research and financial commitment.

Keywords: antibacterial biosimilars; antifungal biosimilars; antimicrobial peptides; antiviral biosimilars; infection management; monoclonal antibodies; therapeutic proteins.

Figure 1

Antiviral activity of mAbs. mAbs possess the capacity to directly influence viral pathogenesis through various mechanisms. (A). The attachment of a neutralizing antibody to the virion can obstruct the binding to target cells and/or inhibit the fusion process. (B). The binding of antibodies tags pathogens for destruction, thereby promoting their phagocytic uptake. Created in BioRender 201 [37].

Figure 2

Multiple mechanisms of action of interferons against viruses. Interferons are produced in response to viral infection. They are warning signals to neighboring cells, which are stimulated to put up barriers to protect from viral entry (a). Interferons also signal infected cells to undergo cell death (b). Finally, they recruit white blood cells to destroy the pathogens and stimulate long-term memory (c). For example, IFN-α and IFN-β utilize mechanisms a and b, inducing an antiviral state in neighboring cells and promoting apoptosis of infected cells. IFN-γ employs the third mechanism, recruiting immune cells to stimulate long-lasting immunity. Created in BioRender [48].

Figure 3

Mechanism of action of viral entry inhibitors. Left: Early steps of the viral life cycle. (1) The virus, using spike proteins or other receptors, binds and interacts with receptors on the target cell surface. This triggers receptor-mediated endocytosis (2). Once inside, the contents, including the genetic material of the virus, are released into the cell and infection continues (3). Right: Entry-inhibitors, such as Enfuvirtide, obstruct the interaction between viral and host cell receptors, consequently impeding the process of viral entry and preventing infection. Created in BioRender 201 [54].

Figure 4

The mechanism of action of membrane-disrupting AMPs. Some AMPs, like defensins, exert their effects through the disruption of bacterial cell walls via a two-step process. The initial step involves the attraction of the AMP to the membrane through electrostatic attraction to the transmembrane electric field (1), which then leads to the incorporation of the AMP into the lipid bilayer, resulting in the formation of a pore (2). Created in BioRender [82].

Figure 5

Two different models of cell wall destruction by AFPs. For the carpet-like model, the AFPs attach to the membrane, aggregate, and insert themselves into the lipid bilayer. They are aligned so that the hydrophobic region contacts the membrane lipids, and the hydrophilic region forms pores. For the barrel wall model, the peptide forms a large, parallel layer across the surface to destroy the membrane. This figure was modified from reference [102] under the Creative Commons Attribution CC BY 4.0 License.

Figure 6

Process development of biosimilars. (1). The genetic material of a biosimilar is integrated into an expression vector, then transfected into a host cell for production. (2). The lead cell line of a biosimilar is cultivated on a laboratory scale, wherein the cell culture parameters are optimized to enhance yield. (3). Isolation, which uses various filtration steps and purification via chromatography, is optimized to maximize purity. (4). The ultimate biosimilar products are manufactured and distributed. Created in BioRender [128].