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British Journal of Healthcare and Medical Research - Vol. 9, No. 1
Publication Date: February, 25, 2022
DOI:10.14738/jbemi.91.11721. Rao, J. R. (2022). Industrial experience - An opinion article: Can Natural Structural Analogues of Antimicrobials be Repurposed as
External Use Disinfectants? A Small Scale Industry’s Experience in India During Pandemics. British Journal of Healthcare and Medical
Research, 9(1). 70-76.
Services for Science and Education – United Kingdom
Industrial experience - An opinion article
Can Natural Structural Analogues of Antimicrobials be
Repurposed as External Use Disinfectants? A Small Scale
Industry’s Experience in India During Pandemics
Juluri R. Rao
Environmental Microbiology, Agri-Food & Biosciences Institute
Newforge Lane, Belfast BT9 5PX, UK
ABSTRACT
This opinion article highlights the experience of a small group of textile
entrepreneurs in India, who despite the economic downturn during the pandemic
crisis, and diversified to a small scale healthcare industry. By not only having
innovated a way out of their set-backs, but also utilising a proof of concept industry- led study, they have repurposed macromolecular natural product structural
analogues for external use applications such as protective antimicrobial coating for
domestic and healthcare fabric laundering, and as disinfectant in places with a
heavy footfall (e.g. mass / rapid transport systems, hospitality sector) in developing
nations. Furthermore, natural antimicrobial analogues supplied at nanomolar
dosage, this prototype product adds no burden to either environmental toxicity or
antimicrobial resistance. A collaborative interplay of the industry with academia
and medical researchers would heighten the science of this industries unique
approach of a different kind of ‘ drug repurposing’ to underpin a practical working
solution for long-term disinfection beyond the contagion pandemics to both public
and healthcare utilities in economically challenged developing nations.
Key words: Repurposed oral drugs; Structural analogues of natural product
Antimicrobials; External use non-alcoholic disinfectants formulations; Industrial
experience in a developing nation
INTRODUCTION
Over the last 12 years, coming from an environmental microbiologists looking glass, I have been
involved in a raft of projects with my interactive colleagues comprising clinical microbiologists,
healthcare practitioners at Northern Ireland Public Health laboratories, School of Experimental
Medicine, Queens University, Belfast and biomolecular, biomedical scientists at University of
Ulster featuring in my citations, and last but not the least valuable input by scientists from
international universities (e.g. Japan, China). We were essentially focussed on exploring both
the knowledge on herbal medicines [1] to fight antimicrobial resistance (AMR) [e.g. 2, 3], and
seek potential alternative complementary medicines for combating the AMR menace that is
costing our healthcare within UK. This aspect has unequivocally been at the heart of our
scouting for the local native plant and microbial resources which provided novel insights into
plant health and biomedical applications [4]. The natural product antimicrobial constituents
were assessed using standard protocols as well as novel bioimaging techniques [5] for
antagonistic microbe-microbe interplay and/or antibiosis [e.g. 6-9], antimicrobial efficacies
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Rao, J. R. (2022). Industrial experience - An opinion article: Can Natural Structural Analogues of Antimicrobials be Repurposed as External Use
Disinfectants? A Small Scale Industry’s Experience in India During Pandemics. British Journal of Healthcare and Medical Research, 9(1). 70-76.
URL: http://dx.doi.org/10.14738/jbemi.91.11721
against clinical pathogens [10-14], and antibiotic effects of native plant and fungal
protein/peptide extracts [e.g. 15]. More recently we demonstrated that structural analogues of
plant phytohormone (gibberellins) showed inhibitory effects at nanomolar concentrations of
their enantiomers upon a wide range of clinical and plant pathogens (16).
INDUSTRIAL EXPERIMENTING AND EXPERIENCES – TRIALS AND TRIBULATIONS
“Crisis is a time for innovation”
To this end, in this opinion article I wish to bring a small scale industry’s efforts who were
former textile industry specialists in South of India and were experiencing serious setbacks in
their own fabric trading due to / during the height of pandemic lockdowns and factory closures.
The small scale industry followed the mantra “recession is a time for innovation” [17] and as to
why it is more important for small-medium businesses particularly to focus on diversifying into
healthcare innovation and as a launch-pad out of the covid-19 crisis [18]. Thus, undaunted by
such challenges as the covid-driven nuances to their fabric businesses, the small scale industry
launched a new start up small scale healthcare industry, India (SSHI) www.lokkavach.com with
a view to ‘re-invent’ their textile expertise and twinning it with the idea of formulating an
environmentally sustainable, health and safety compliant new disinfectant formulations that
may be targeted for use as antimicrobial coating for daily use fabrics as well as disinfectant
conditioner whilst bulk laundering in healthcare attires, and as surface disinfectant in public
transport environments. To this end, the small scale industrialists in India, prompted in part by
my recent evidence based research in natural product structurally active antimicrobials sought
my scientific advice, and in the light of their synchronous feasibility studies of ‘repurposing’
naturally occurring structural analogue chemical entities for external disinfection purposes,
purportedly at health and safety compliant and environmentally safe nanomolar levels.
Proof of concept of a small scale start up industry in healthcare
In a proof of concept, industry-led study, the SSHI produced a new formulation YUDEF (under
non-disclosure, trade secret and patent pending agreements). From the industry’s generic
disclosures available to me at the time of writing this opinion article, it contains ca. 250-400
ppm of Quaternary Ammonium Compounds aka QACs for short. However, it is a well- documented fact that QACs are generic disinfectant agents are cheap, and extensively used
against environmental contagions [e.g. 19], but lesser effective against spore formers and
viruses. Thus the innovative step by the industry-led study involved fortifying the QACs with
naturally occurring (organic) compounds referred to as AVCR (Anti-Viral Composites of natural
product structural analogues) for exhibiting robust contagion defence against stubborn
bacteria, fungi and also expressing antiviral effects. These were sourced via structural biology
methods [e.g. 20] for matching the chemical analogues of approved drug with proven broad
spectrum antimicrobial efficacies. As a small scale non-medical industry, they regarded this
step to be a practicable fast-track approach than to be trialling via high throughput, cost- intensive screening route on 1000s of potential candidates. For a prototype product, the choice
was narrowed to a handful of macromolecules not limited to but inclusive of peptides, aromatic
amines, lactones etc. naturally occurring macromolecular ‘structural repurposed drug
analogues’.
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British Journal of Healthcare and Medical Research (BJHMR) Vol 9, Issue 1, February - 2022
Services for Science and Education – United Kingdom
In vitro study upon the 'anti-viral’ performance of ‘repurposed drug analogues’
An in vitro study upon the 'anti-viral’ performance of ‘repurposed drug analogues’ incorporated
in face masks' at nanomolar (ca 10-5mM) concentration and fabric pieces supplied by SSHI, was
conducted at a local vaccines and viruses research centre, Tamil Nadu Veterinary and Animal
Sciences, Chennai, India (TANUVAS) using a type species of corona virus (Rat Coronavirus)
offering such testing of disinfection products services at the time serial lockdowns in India due
to covid-19 pandemics in 2020. With apparent restrictions for testing covid-19 itself as a strain
at the time, the proof of concept of the efficacy of the repurposed YUDEF product study was
conducted on L2p.196 cell line, which is susceptible for rat coronavirus infection. A preliminary
cytoxicity study was also performed on the SSHI’s formulation. Concentrations lower than the
one causing cytoxicity was taken up for in vitro study. The chosen concentration was mixed
with 10e4.3 TCID50 of virus in equal volumes and infected on to cell cultures. The concentration
that caused complete abrogation of virus-induced cytopathic effects i.e. CPE (implying a
reduction of 4.0 log of virus infectivity or 99.9% disinfecting efficiency) was considered as
minimal disinfection concentration. The cytotoxicity of SSHI’s formulation was also ascertained
using a spray of the virus on an impervious surface followed by anti-viral formulation
treatment. The dried up surface was washed and assessed for the presence of infectious virus.
The antimicrobial tests on YUDEF product were compliant to EU accreditation tests set at
EN14476 and ISO 18184 guidelines for virus reduction (up to >99%) on coated soft fabric and
hard surfaces, and ascertained to be non-toxic (Biotech report, supplementary data). The Irish
Equine Centre www.irishequinecentre.ie, one of the few in Europe offering antiviral testing
services for such prototype products on fabrics during the pandemics; they corroborated
independently that the YUDEF product has strong antiviral efficacy. Together with other
laboratory test reports (supplementary data pdf) provide unequivocal evidence that the SSHI’s
natural prototype product drug analogue repurposed product (YUDEF) possesses broad
spectrum antimicrobial protection on fabrics when challenged via a range of standard microbial
inhibitory assays and testing procedures.
DISCUSSION
Drug repurposing model for oral use
From the very outset, the SSHI have taken a cue from their ‘big brother’ business leaders such
as pharma companies. For instance, in order to contend with this global health crisis situation,
an almost twin track strategy operates via the development of several effective anti-SARS-CoV- 2 vaccines which are in many ways a re-invention in its molecular medicine value [e.g. mRNA
vaccines (Pfizer, AstraZeneca, Moderna among others)], and repurposed drugs [“The
Repurposing, Focused Rescue, and Accelerated Medchem” (ReFRAME)] approach. This binary
policy will no doubt contribute to the control of SARS-CoV-2 strains global origin variants (e.g.
alpha, beta, gamma, delta, the latest omicron etc.). On-going intense efforts to identify
therapeutic interventions and their efficacies, fitness for purpose initially identified simple
antibiotics e.g. Hydroxychloroquine, Azithromycin [21] for in vitro covid-19 neutralisation
effects. A plethora of higher precision chemical entities (ca. 12,000 small-molecules [22] also
augur well for real-time covid patient treatment. Other repurposing of FDA approved drugs
include monoclonal antibody (MABs) (e.g. Casirivimab/Indevimab as intravenous (IV) or
subcutaneous (SC) drugs (Roche), Molnupiravir, (Merck, Sharp and Dohme (MSD) and
Ridgeback Biotherapeutics, Paxolovid (Pfizer), oral tablet form of drugs repurposed for covid
treatment.