Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface

Abstract

Emerging infectious diseases present great risks to public health. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become an urgent public health issue of global concern. It is speculated that the virus first emerged through a zoonotic spillover. Basic research studies have suggested that bats are likely the ancestral reservoir host. Nonetheless, the evolutionary history and host susceptibility of SARS-CoV-2 remains unclear as a multitude of animals has been proposed as potential intermediate or dead-end hosts. SARS-CoV-2 has been isolated from domestic animals, both companion and livestock, as well as in captive wildlife that were in close contact with human COVID-19 cases. Currently, domestic mink is the only known animal that is susceptible to a natural infection, develop severe illness, and can also transmit SARS-CoV-2 to other minks and humans. To improve foundational knowledge of SARS-CoV-2, we are conducting a synthesis review of its host diversity and transmission pathways. To mitigate this COVID-19 pandemic, we strongly advocate for a systems-oriented scientific approach that comprehensively evaluates the transmission of SARS-CoV-2 at the human and animal interface.

Keywords: COVID-19; One Health; SARS-CoV-2; animals; coronavirus; host diversity; humans.

Figure 1

A conceptual diagram displaying the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among humans and various animal hosts. (A) Horseshoe bats (Rhinolophus affinis) are the most likely animal reservoir and ancestral hosts of the SARS-like CoV that gave rise to SARS-CoV-2 [53,105]. (B) A multitude of animals including mammals, birds, and reptiles have been proposed as potential intermediate hosts [38,39,41]. (C) SARS-CoV-2 was first reported in humans in December 2019 in Wuhan, China [106]. (D) Successful laboratory infections of SARS-CoV-2 have been reported in the following mammals: domestic dogs, domestic cats, ferrets, rabbits, raccoon dogs, hamsters, mice, tree shrews, cattle, and several species of non-human primates [107,108]. (E) In January 2020, the World Health Organization (WHO) first reported that human-to-human transmission of SARS-CoV-2 is feasible [109,110]. (F) Natural infections of SARS-CoV-2 in animals transmitted from humans (i.e., reverse zoonosis or anthroponosis) have been detected in domestic dogs and cats, domestic mink, ferrets, mice, hamsters, captive gorillas, and captive large cats (e.g., tigers and lions) [111,112]. (G) Evidence of SARS-CoV-2 spillback from domestic minks to humans and intraspecies transmission of SARS-CoV-2 among minks has been detected [46,47]. At this time these are the described transmission pathways and animals.

Figure 2

Structure of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The virus is built up of four major structural proteins: the spike (S) protein; the nucleocapsid (N) protein; the membrane (M) protein; and the envelope (E) protein. The S protein is responsible for facilitating the entry of the CoV into the target cell. The routes employed by SARS-CoV include endocytosis and membrane fusion. The route employed by SARS-CoV-2 is via endocytosis; whether SARS-CoV-2 enters cells by membrane fusion is not known. Binding of the S protein of SARS-CoV to angiotensin-converting enzyme 2 (ACE-2) leads to the uptake of the virions into endosomes, where the viral S protein is activated by the pH-dependent cysteine protease cathepsin L. Activation of the S protein by cathepsin L can be blocked by bafilomycin A1 and ammonium chloride, which indirectly inhibit the activity of cathepsin L by interfering with endosomal acidification. Chloroquine and hydroxychloroquine are weak bases that diffuse into acidic cytoplasmic vesicles such as endosomes, lysosomes, or Golgi vesicles and thereby increase their pH. MDL28170 inhibits calpain and cathepsin L. SARS-CoV can also directly fuse with host cell membranes, after processing of the virus spike protein by transmembrane protease serine 2 (TMPRSS2), a type II cell membrane serine protease. Camostat mesylate is an orally active serine protease inhibitor. Figure and caption sourced from Ky and colleagues [114].