# Biosurfactants' Potential Role in Combating COVID-19 and Similar Future Microbial Threats
## 2 Approaches That Can Use Biosurfactants in Outbreak Prevention and Management
### Therapeutics
#### 2.1.6 Drug Development  
Chemical modifications of biomolecules, especially lipids, have numerous applications in chemistry and pharmacokinetics. The hydrogen atom deuterium is a stable hydrogen isotope, having both a proton and a neutron within its nucleus. Deuterium oxide (D\({}_{2}\)O) is well known in medicinal chemistry, and it is being used in the modification of various biomolecules for pharmaceutical purposes [56]. Deuterated biosurfactants are produced by bacteria strain AD7 of _Pseudomonas aeruginosa_ with varying levels of D\({}_{2}\)O and carbon substrates. These molecules are safer and can be used to monitor drug metabolism within biological systems. These are used as substrates, therefore the level of deuteration of the biosurfactant can be manipulated. The flexibility of a biosurfactant used as an adjuvant can enable modifications on antibiotics and other drugs, which can result in the improved performance of an existing antibiotic, or even restrict the development of antimicrobial resistance with the possibility of using a small dose of the drug [57]. Besides pharmacokinetics, the antimicrobial properties of biosurfactants can be exploited in drug development. _Rlodococcus fascians_ BD8 isolated from arcite soil was found to produce a trehalose lipid biosurfactant with antimicrobial activity against the drug-resistant bacteria _Vibrio harveyi_ and _Proteus vulgaris_. Partial inhibition at 11-34% was observed on other Gram-positive and Gram-negative bacteria, as well as 30% inhibition of _Candida albicans_ at 0.5 mg/mL concentration [58]. In combination with existing drugs, synergistic effects between biosurfactants and antibiotics have also been reported. Methicillin-resistant _Staphylococcus aureus_ was inhibited by using a joint sophorolipid and tetracycline treatment in vitro. Bacteria inhibition was observed at concentrations below the minimum inhibitory concentration. Understanding the underlying mechanisms of synergy between biosurfactants and antibiotics could prove useful in the development of effective treatments against drug-resistant pathogens [59]. Another way to develop effective treatments is the use of precision antimicrobials. Their applications in personalized medicine as a way of reducing the effects of drugs in the body are rapidly expanding. This novel approach to treating infectious diseases can use biosurfactants [60]. Bacaucin is a peptide biosurfactant isolated from _Bacillus subtilis_ strain CAU21, which was reported to have broad-spectrum antimicrobial properties against Gram-positive bacteria but with haemolytic and cytotoxic effects. When the lipid portion is removed and the ring of the heptapeptide opened, bacaucin-1 is produced, which has more hydrophilic portions exposed, resulting in an overall decrease in the hydrophobicity of the molecule. Bacaucin-1 was selectively active against antibiotic-resistant _S. aureus_ strains through cell membrane disruption, and demonstrated no bacterial resistance and cytotoxicity to mammalian cells in vitro and in vivo [61]. Structural modification of biosurfactants could lead to the development of highly precise drugs which can be used against pathogens sharing many similarities with human cells. Biosurfactants from _Bacillus subtilis_ have also shown in vitro antiviral properties against the enveloped virus species such as herpes, retroviruses, and other non-enveloped viruses. These groups share structural similarity with pathogens such as HIV, MERS, SARS, and Hepatitis. _Bacillus subtilis_ surfactin inactivated the viruses at concentrations of 25 um-80 um. The mechanism of action was through the destruction of viral lipid membranes and capsid [62]. The formation of ion channels in the viral capsids and lipidenvelopes leading to the loss of proteins involved in the process of membrane attachment, fusion and penetration has been reported [63].