Contributions of the international plant science community to the fight against infectious diseases in humans-part 2: Affordable drugs in edible plants for endemic and re-emerging diseases.

The fight against infectious diseases often focuses on epidemics and pandemics, which demand urgent resources and command attention from the health authorities and media. However, the vast majority of deaths caused by infectious diseases occur in endemic zones, particularly in developing countries, placing a disproportionate burden on underfunded health systems and often requiring international interventions. The provision of vaccines and other biologics is hampered not only by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, but also by challenges caused by distribution and storage, particularly in regions without a complete cold chain. In this review article, we consider the potential of molecular farming to address the challenges of endemic and re-emerging diseases, focusing on edible plants for the development of oral drugs. Key recent developments in this field include successful clinical trials based on orally delivered dried leaves of Artemisia annua against malarial parasite strains resistant to artemisinin combination therapy, the ability to produce clinical-grade protein drugs in leaves to treat infectious diseases and the long-term storage of protein drugs in dried leaves at ambient temperatures. Recent FDA approval of the first orally delivered protein drug encapsulated in plant cells to treat peanut allergy has opened the door for the development of affordable oral drugs that can be manufactured and distributed in remote areas without cold storage infrastructure and that eliminate the need for expensive purification steps and sterile delivery by injection.

Affordable oral health care: dental biofilm disruption using chloroplast made enzymes with chewing gum delivery.

Current approaches for oral health care rely on procedures that are unaffordable to impoverished populations, whereas aerosolized droplets in the dental clinic and poor oral hygiene may contribute to spread of several infectious diseases including COVID-19, requiring new solutions for dental biofilm/plaque treatment at home. Plant cells have been used to produce monoclonal antibodies or antimicrobial peptides for topical applications to decrease colonization of pathogenic microbes on dental surface. Therefore, we investigated an affordable method for dental biofilm disruption by expressing lipase, dextranase or mutanase in plant cells via the chloroplast genome. Antibiotic resistance gene used to engineer foreign genes into the chloroplast genome were subsequently removed using direct repeats flanking the aadA gene and enzymes were successfully expressed in marker-free lettuce transplastomic lines. Equivalent enzyme units of plant-derived lipase performed better than purified commercial enzymes against biofilms, specifically targeting fungal hyphae formation. Combination of lipase with dextranase and mutanase suppressed biofilm development by degrading the biofilm matrix, with concomitant reduction of bacterial and fungal accumulation. In chewing gum tablets formulated with freeze-dried plant cells, expressed protein was stable up to 3 years at ambient temperature and was efficiently released in a time-dependent manner using a mechanical chewing simulator device. Development of edible plant cells expressing enzymes eliminates the need for purification and cold-chain transportation, providing a potential translatable therapeutic approach. Biofilm disruption through plant enzymes and chewing gum-based delivery offers an effective and affordable dental biofilm control at home particularly for populations with minimal oral care access.

Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2): an emerging zoonotic respiratory pathogen in humans. (Special Issue: Coronaviruses and COVID-19- Past, Present, and Future.)

Two highly human pathogenic coronaviruses outbreak in the beginning of 21st century i.e. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2002 and 2012 respectively caused high pathogenicity and fatality rates in human populations. Recently, a new coronavirus named as SARS-CoV-2 or nCoV-2019 was first reported in Wuhan, China in December 2019 which is responsible for an acute human respiratory illness referred as Coronavirus Disease (COVID-19), an ongoing pandemic. SARS-CoV-2 is the third known highly pathogenic virus affecting human population. This virus spread globally within few weeks of first identification and nearly 5.52 million confirmed cases with more than 3,47,000 deaths reported as of May 25, 2020. Till date, there are no specific anti-viral drugs, therapies or vaccines to contain and prevent this infectious pathogen outbreak. The global spread of this virus to over 210 countries resulted in both human and economic losses, highlighting the need for an immediate imperative research exploration on prophylactic and therapeutic measures. Current knowledge and understanding of the pathogenesis of similar coronavirus SARS-CoV and MERS-CoV might be helpful for the rapid development of treatment strategies to prevent the further spread of this virus. In this review, we recapitulate the topical understanding on the structure, pathogenesis and epidemiology of SARS-CoV-2 that has emerged as a major health concern worldwide.

Contributions of the international plant science community to the fight against human infectious diseases - part 1: epidemic and pandemic diseases.

Infectious diseases, also known as transmissible or communicable diseases, are caused by pathogens or parasites that spread in communities by direct contact with infected individuals or contaminated materials, through droplets and aerosols, or via vectors such as insects. Such diseases cause ˜17% of all human deaths and their management and control places an immense burden on healthcare systems worldwide. Traditional approaches for the prevention and control of infectious diseases include vaccination programmes, hygiene measures and drugs that suppress the pathogen, treat the disease symptoms or attenuate aggressive reactions of the host immune system. The provision of vaccines and biologic drugs such as antibodies is hampered by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, particularly in developing countries where infectious diseases are prevalent and poorly controlled. Molecular farming, which uses plants for protein expression, is a promising strategy to address the drawbacks of current manufacturing platforms. In this review article, we consider the potential of molecular farming to address healthcare demands for the most prevalent and important epidemic and pandemic diseases, focussing on recent outbreaks of high-mortality coronavirus infections and diseases that disproportionately affect the developing world.

Rapid and Scalable Production of Functional Anti-Coronavirus Monoclonal Antibody CR3022 in Plants (preprint)

Severe acute respiratory syndrome coronavirus-2 is responsible for an ongoing global outbreak of coronavirus disease (COVID-19) and represents a significant public health threat. The rapid spread of COVID-19 necessitates the development of cost-effective technology platforms for the production of diagnostic reagents/biopharmaceuticals for COVID-19. We explored the possibility of producing an anti-SARS-CoV monoclonal antibody (mAb) CR3022 and the receptor binding domain (RBD) of SARS-CoV-2 in Nicotiana benthamiana. Both RBD and the mAb were transiently expressed with the expression of 8μg/g and 130μg/g leaf fresh weight respectively. The plant-purified mAb binds to SARS-CoV-2, but fails to neutralize it in vitro. This is the first report showing the functional characterization of an anti- SARS-CoV mAb CR3022 in plants. Overall these findings showed that plants are a promising platform to produce anti-SARS-CoV mAb to use as a research reagent or a biotherapeutic in a cost-effective manner, which is especially important to developing economies during epidemics.