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

Abstract

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.

Keywords: COVID-19; HIV/AIDS; Molecular farming; SARS-CoV-2; plant-made pharmaceuticals.

Figure 1

The three major molecular farming platforms are transient expression, transgenic plant cell suspension cultures and transgenic plants (Huebbers and Buyel, 2021), the latter either grown in containment or in the open field (bold text, thick arrows). The relative advantages and disadvantages of the three platforms are shown in terms of speed (the faster the better), scalability (the larger the better, generally inversely related to costs) and containment (the more contained the lesser the regulatory burden) with separate indicators for transgenic plants grown indoors and outdoors. Four additional minor or emerging platforms are also shown (regular text, thin arrows). Plant cell suspension cultures are usually transgenic cell lines, but transient expression is also possible (Sukenik et al., 2018) and has been realized in the form of plant cell packs for the high‐throughput and highly automated testing of expression constructs with immediately scalable expression (Gengenbach et al., ; Rademacher et al., 2019). Transgenic organ cultures such as hairy roots can be regarded as an extension of the cell suspension culture concept because the organ cultures are likewise grown in containment in bioreactors (Doran, ; Wongsamuth and Doran, 1997). Variants on the theme of transgenic plants include transplastomic plants, where the transgene is inserted into the plastid genome rather than the nuclear genome (Bains et al., ; Berecz et al., ; Bock, ; Zhang et al., 2017), and rhizosecretion, in which proteins are secreted by the roots of plants into the hydroponic medium, so that aggressive extraction methods are unnecessary (Drake et al., ; Madeira et al., 2016a,b). The figure includes images from Biorender (https://biorender.com/).

Figure 2

Chemical structures of (a) chloroquine, (b) hydroxychloroquine, (c) oseltamivir, (d) dexamethasone and (e) artemisinin

Figure 3

Delivery of ACE2/Ang1‐7 expressed in chloroplasts for the treatment of COVID‐19. (a) Orally delivered ACE2 and its product Ang 1–7 attenuate pulmonary hypertension (PH), reduce RV systolic pressure, RV hypertrophy, fibrosis and pulmonary vessel wall thickness in a rat model, which are the symptoms observed in COVID‐19 patients. (b) SARS‐CoV‐2 binds to the ACE2 receptor in order to enter cells. ACE2 converts Ang I and Ang II to Ang 1–9/Ang 1–7 in the renin–angiotensin system pathway. Oral delivery of plant‐derived ACE2 has the potential to block SARS‐CoV‐2 entry into human cells by competing for the same receptor and also increases the concentration of beneficial Ang 1–7. This figure is modified after Daniel et al. (2021). Abbreviations: ACE = angiotensin‐converting enzyme, Ang = angiotensin, AT1R = angiotensin receptor type I, AT2R = angiotensin receptor type II, LV = left ventricle, MasR = Mas receptor, RV = right ventricle