Fermentation for Antiviral Agents

As a leading CDMO, BOC Sciences provides custom fermentation service for antiviral agents development. Based on comprehensive platforms and GMP-complied quality system, we focus on fermentation-related projects to meet the needs of our pharmaceutical industry clients.

Introduction

The diversity and complexity of natural products (NPs) provide significant efficacy and specificity for targeting viral infections and serve as an excellent source of antiviral drugs. Due to the low abundance in natural hosts, production of antiviral natural products in microorganisms by biosynthetic pathways is a promising solution. With the development of metabolic engineering and microbial fermentation technologies, heterologous synthesis of antiviral agents using genetically engineered microorganisms offers several significant advantages over plant-derived and chemical synthesis, such as the ability to biosynthesize complex natural products that are often difficult to chemically synthesize, cost-effective microbial platforms, renewable feedstocks, and ease of large-scale production of target products.

Viruses cause a variety of human diseases, including cancer, and some well-known viruses include hepatitis B (HBV) and hepatitis C (HCV) viruses, human immunodeficiency virus (HIV), and influenza viruses. Most antiviral drugs work by inhibiting viral DNA synthesis, and these drugs are chemically similar to normal DNA nucleosides. A variety of natural products have been reported to have potent antiviral activity or to be promising sources of antiviral drugs. For example, hydroxychloroquine, artemisinin and ivermectin, nucleotide analogues (e.g. spongouridine derived from natural sources) have been found to have antiviral properties.

Fermentation Production of Antiviral Agents

Fermentation for Antiviral Agent

The selection of a suitable microbial host is the first key factor in the production of natural antiviral agents. Escherichia coli and Saccharomyces cerevisiae are the two most commonly used hosts for fermentative production of valuable compounds. Microorganisms can be used as cell factories for low-cost, scale-up fermentation production of antiviral agents in processes involving strain improvement, metabolic engineering, fermentation, fermentation downstream purification and isolation, and analysis and characterization of target antiviral agents.

Our Services

Host Selection

Lab host strain evolution
Strain improvement
Host cell selection

Metabolic Engineering

Mitigation of transcriptional repression
Blocking competitive pathways
Modular pathway engineering
Overexpression of key enzymes
Transporter engineering
Improving the catalytic efficiency

Fermentation

Different incubation modes
Dissolved oxygen control
Temperature and pH control
Optimization of culture medium
Downstream process development
Fermentation scale up

Classification of Fermented Antiviral Agents

Fermented antiviral agents can be classified into aromatic compounds, nucleotide analogs, polyketides, terpenoids , and alkaloids based on their chemical nature.

Nucleotide analogs

Nucleosides are a promising class of natural compounds. Both bacteria and eukaryotes have the capacity for nucleoside biosynthesis. Natural nucleosides have a variety of structures, which are part of nucleotides, DNA, RNA and coenzymes. Drug development based on natural compounds is a classical approach, such as the modification of natural nucleosides to develop antiviral drugs.

Terpenoids

Terpenoids are the most abundant compounds among natural products and are important secondary metabolites in plants. Terpenoids exert antiviral effects mainly by blocking viral DNA replication and transcription. For example, the monoterpenoids isoborneol and borneol have strong activity against herpes simplex virus 1 (HSV-1); Artemisinin and its derivatives show significant inhibitory activity against both HBV and HCV.

Alkaloids

Alkaloids are a large group of structurally diverse natural products of microbial, plant and animal origin. Many alkaloids possess potential antiviral activity against different DNA and RNA viruses.

Alkaloid	Source	Virus	Activity
Anisomycin		DENV, ZIKAV	Inhibits replication
Camptothecin	Camptotheca acuminata	EV71	Inhibits viral RNA replication and translation
Colchicine	Haplophyllum tuberculatum, Colchicum autumnale	HIV 1	Inhibit replication by DNA intercalation
Gliotoxin		HI	Inhibits intracellular replication

Table 1. Examples of alkaloids with antiviral activities.