**4. Antiviral strategies**

*Saccharomyces*

model organism until 2002 [44, 45].

Human serum albumin Blood

**Bioparhamaceutical** 

Human parathyroid

Purified protein for

hormone

vaccines

**products**

this yeast could discover the process of diseases because of the conservation of molecular interactions from yeast to humans [21, 22]. On the other hand, *S. cerevisiae* can be an essential organism for recombinant protein production for pharmacy. It has full cellular organelles and membrane compartments that produce many eukaryotic proteins, including humans' [23]. Initially, the essential biopharmaceuticals insulin and its analogs have been produced by *S. cerevisiae*. Researchers have reported other important biopharmaceuticals such as the human serum albumin, hepatitis vaccines, and virus-like particles for vaccination (**Table 1**). Also, several medicines have been produced with *S. cerevisiae* until 2012 reported by the European Medicines Agency [18]. Furthermore, current studies showed that metabolic engineering pathways and optimization procedures of *S. cerevisiae* are essential for producing recombinant proteins for pharmaceuticals and biomedical areas [18, 19]. *S. cerevisiae* carries out human-like glycoprotein that is efficient for producing recombinant proteins. Protein secretion of *S. cerevisiae* is complex processing that follows as transcription, translation, translocation, post-translational modifications, folding, peptide cleavage, glycosylation, sorting, and secretion. This important organism enables genetic modifications. It was reported that the first eukaryotic organism sequenced DNA in *S. cerevisiae* [41]. Due to the protein misfolding and aggregation*, S. cerevisiae* has been used as a model organism. Nevertheless, *S. pombe* has been accepted as a model organism together with *S. cerevisiae*. This fission yeast is used as a successful host. It was reviewed that *S. pombe* and generated strains have significant facilitation for producing drug glucuronides [42, 43]. The classical yeast genetics approaches can be described for *S. pombe*. It has been accepted as the most ancient yeast molecule. However, *S. pombe* has been more advanced evolutionarily than other yeasts. *S. pombe* has become a

Recombinant proteins are recognized as an important part of the drug industry. Among these proteins, Saccharomyces has greater attention than others due to their eukaryotic properties, easy genetic manipulation, and capable of modifications. *S. cerevisiae* emerges as the most common host to express heterologous genes and therapeutic proteins [46]. This organism may provide a simple background for isotype expressions, and thereby drug metabolism studies can be easily associated

Payne et al. [24]

Protein Hadiji-Abbes et al. [30], Zhang et al. [31], King et al. [32], Kaslow and Shiloach [33], Fazlalipour et al. [34].

Recombinant proteins Protein Huang et al. [18], Ferrer-Millares et al. [19], Ma et al. [25], Cino [26]

with genome screens, underlying toxicity, and encoded genomes.

factors

Insulin Hormone Martinez et al. [27] Glucagon Hormone Egel-Mitani et al. [28]

*Examples of bioparhamaceutical products of Saccharomyces.*

**Category References**

Hormone Song et al. [29]

Virus like particles Protein Jacobs et al. [35], Kim et al. [36], Kim et al. [37]. Gene expression systems Gene Malak et al. [38], van Ooyen et al. [39], Vierira Gomes et al. [40].

**62**

**Table 1.**

While the vaccines currently available have proven invaluable in the fight against infectious diseases and eradicating viruses, there are many drawbacks to the current vaccine preparation or application regimen despite these successes. Certain limitations of conventional vaccines require multiple adjuvants and injections to induce a necessary or optimal immune response. Another reason is the constant increase in the number of post-vaccination allergic reactions or hypersensitivities in a specific group of people [47, 48].

Today, there are several critical viral diseases such as human hepatitis B and C, immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus (SARS), coronavirus-disease 2019 (COVID19), etc. Due to the inadequacy of treatment options for these infections, new antiviral strategies and model organisms, particularly yeast, were of interest to the researchers.

Yeasts have a delivery system for nucleic acids, and thus they can be an alternative for virus description. Besides, a humanized yeast system was identified for yeast/virus systems to study diseases [49]. Yeasts are used for subunit vaccine formulations with producing antigens against viruses. It was reviewed that yeast can be used for vaccine development in such strategies; whole recombinant yeast, virus-like particles, yeast display, and purified protein immunogens [50]. Among yeasts, *S. cerevisiae* has been accepted as a versatile model organism for viruses' research, from the wire of public health to vaccine production.

Rosenfeld and Racaniello [51] reported that hepatitis C virus (HCV) was demonstrated in *S. cerevisiae*, and all proteins for the virus were encoded. Another study reported that *S. cerevisiae* could safely express the hepatitis B surface antigen in prophylactic vaccines [52]. Researchers observed that yeast could help clarify the function of viruses' proteins with dissection of RNA viruses' life cycle [53, 54]. Nevertheless, several protein immunogens can be purified from Saccharomyces. These immunogen proteins derived from yeasts are associated with virus-like particles. Virus-like particles can provide an alternative for viruses, and FDA approved this vaccine for hepatitis B and papillomavirus [55]. Also, the circumsporozoite protein derived from *S. cerevisae* is an immunodominant antibody of malaria. This preparation increased the antibodies and thereby neutralized the sporozoites [56]. Due to the yeast membrane permeability, *S. cerevisiae* enables entry to the chemical compounds and provides virus-host interactions. Some researchers showed that beta-glucan of the yeast cell wall could provide the immune response that important for vaccine development [57].

All things considered, the yeast-based carrier system can be a potential model to develop the vaccine insights of virus-host interactions. The yeast strategies can improve the recognition of pathogen antigens peptides, activate the immune response, and also modulate the yeast-based vaccines. Researchers for further pioneering findings have still endured the studies.

### **5. Future perspectives**

There have been many illnesses that have not been controlled by vaccination and new ones as well. Mutation, genetic exchange, environmental and interspecific transference, or human contact are the most emerging diseases. However, new scientific technologies, model organisms and a number of researchers have proven beneficial to vaccination strategies. In this respect, it is possible to observe yeasts for the upcoming vaccines for several diseases.

Yeast engineered to the virus has been accepted as an ideal therapeutic approach. This vaccine's strategy is improving humoral immunity due to the ability of yeast to the generation of immune responses.

There is a numerous increasing study to obtain the vaccine strategy of yeasts. Studies in yeast proteins and cell wall components, including beta-glucan, may become more critical for vaccine strategies under different phases of clinical trials on animals or humans. According to the essential features of yeast, the yeast-based vaccine strategy is being necessary for vaccine development. It has foreseen that diversity of yeast strains will improve in the future.
