Viruses are obligate intracellular parasites having ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) with single or double strands enclosed within a protective protein shell (capsid). The capsid has oligomeric structural subunits constructed with helical, icosahedral or complex symmetry. It shields the genome from lethal agents. Viruses are acellular, lacking enzyme machinery for metabolism and ribosome for protein synthesis, but carry their own genome during transmission [26]. They depend on host cells for replication, genome transcription and translation of mRNA transcripts into proteins. Viruses are enveloped, filamentous, isometric (icosahedral) or head–tail shaped. RNA viruses are less stable than DNA viruses [25]. Both have divergent genome sizes of diameter 20–400 nm. Using genomic sense or polarity system, RNA viruses belong to two groups: positive-strand and negative-strand viruses [26]. Most ssRNA viruses have ∼6–14 positive charges on sequence adjacent to the interior of the capsid at the amino or C-terminal ends. CoVs are enveloped RNA viruses and have been a major public health emergency for decades. Approximately 70% of viruses are ribonucleic acid (RNA) viruses and are responsible for almost 44% of emerging infectious diseases under various ecological zones worldwide. Incidence of lethality has remained high since 1931 when the first human coronavirus (HCoV-229E) was discovered, and enteric CoV was isolated from turkeys in 1951 [26]. The novel coronavirus (SARS-CoV-2) exhibits bulbar projections produced from the spike of glycoprotein (peplomers) on the capsid. Its zoonotic nature implies that both humans and animals are vulnerable to infection. The susceptibility of nonhuman species has been confirmed by sequencing oral and nasopharyngeal swab specimens from Syrian hamsters, bats, cats, dogs, ferrets, lions, mink and a few companion animals. Analysis of samples from the upper respiratory tract of ferrets equally confirms the prevalence of SARS-CoV-2 infection, but weak replication of the same strain was found in chickens, dogs, ducks and pigs. However, the high nucleotide similarity index (96.2%) of SARS-CoV-2 with coronavirus RaTG13 shows that horseshoe bats (Rhinolophus spp.) harbour the same viral strain [26,27,28].

Aside from COVID-19, Ebola, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are common RNA viral diseases that confer burdens of illnesses across species [5]. Complications emanating from such infections are heterogeneous across gender and age groups but correlate with morbidity indices. Comorbidity is the coexistence of one or more diseases simultaneously with a primary medical condition in a patient. Most patients that died of COVID-19 had comorbid complications that worsened their chances of survival. While elderly people with underlying conditions are prone to higher risks, children infected with the virus manifest mild or no symptoms. The majority of patients in intensive care units or under invasive mechanical ventilation exhibiting a high prevalence of comorbidities (46–86.2%) due to extreme obesity (BMI ≥ 30), chronic renal failure, asthma, hypertension, type 2 diabetes, ischemic heart disease and chronic obstructive pulmonary disease did not survive [29]. General feeling of malaise, fever, dry cough, anorexia, pneumonia, abnormal heartbeats, shortness of breath, lymphopenia and high viral loads linked with cytokine activation and histopathological changes are concomitantly detected during clinical tests [30]. Loss of smell or taste and acute confusional state (delirium) coupled with disorientation, psychomotor changes and clouding of consciousness are newly detected COVID-19 symptoms. Recent findings affirm that patients suffering from severe SARS-CoV-2 infection have elevated levels of C-reactive protein, ferritin and D-dimer; high neutrophil-to-lymphocyte ratio; and increased levels of inflammatory cytokines and chemokines [31]. The overlapping effects of these conditions impact comorbidity–polypharmacy score, cumulative illness rating and mortality. Many people and livestock animals are still vulnerable to coronavirus infection. To ensure animal welfare and efficient biosecurity measures in the agro-environment, it is necessary to use novel biosensors for viral detection, tracking immune response and identifying high-risk zones to minimise exposure to viral aerosol and microdroplets from humans, livestock, fomites or passive vectors.

Cellular receptors of human coronaviruses (HCoVs) belong to the membranous ectopeptidase family [4,22]. Receptors are macromolecules (glycoproteins) mediating biological processes to bind signaling molecules (ligands) intracellularly or extracellularly for initiating cellular responses. Intracellular receptors exist within the cytoplasm and bind to hydrophobic ligands roving across the plasma membrane. Cell-surface receptors (transmembrane receptors) are membrane-anchored proteins that bind to ligands on the surface of the cell to perform signal transduction functions [4,13]. Receptors have a transmembrane domain and an extracellular domain with a ligand binding (allosteric binding) site. The binding of receptors to ligands occurs at agonistic (ligand-binding) and antagonistic (ligand-blocking) sites. These include ligand-gated channels, G-protein-coupled receptors and enzyme-associated receptors. An enzyme-linked receptor is an integral membrane protein performing catalytic and receptor functions. Receptors undergo conformational changes to elicit responses by actively binding to or dissociating from ligands in cellular signaling or gated ion channels. Ligand-gated ion channels or ionotropic receptors are transmembrane ion-channel proteins that open to allow passage of Na⁺ K⁺, Ca²⁺ and/or Cl⁻ ions through the membrane in response to the binding neurotransmitter. G-protein-coupled receptors such as 7T-transmembrane domain receptors, heptahelical receptors, serpentine receptors and G-protein-linked receptors detect molecules extracellularly and activate internal signal transduction pathways and cellular responses [44].

Viruses use multiple molecular species as receptors for infecting target cells. These receptors consist of sialic acid (C₁₁H₁₉NO₉), glycosaminoglycans (negatively charged polysaccharides) and cellular adhesion molecules (intercellular adhesion molecules, vascular cell adhesion molecule-1), acetylcholine receptors, chimeric antigen receptors, interleukin-2 (IL-2) receptors, complementary receptors, growth factor receptors and neurotransmitter receptors [45,46,47]. Genome encoding occurs after viral invasion to elicit gene expression, accessory proteins and adaptation to the host. SL-CoV and SARS-CoV share similar genomic sequences and highly conserved gene products in the receptor-binding domain of the N-terminal region of S-proteins. A virus is unlikely to establish and replicate itself in the host without evasion or antagonism. As the mechanisms of attachment, intracellular trafficking, uptake and incursion into cytosol are affected by the bond between virus and receptor, the synergy between them even heightens the probability of infection occurring and activity of spike protein in the process. Whilst host cells exert defense mechanisms for rapid detection of infection or suppression of immune response, viruses have ways of evading them through pattern recognition receptors (PRRs). Upon infection, PRRs sense nucleic acids in the cytoplasm or nucleus to activate antiviral innate immunity. RNA viruses use non-primer-dependent mechanisms for replication, distortion of RNA recognition and antiviral signaling. SARS-CoV-2 exploits the angiotensin-converting enzyme-2 (ACE-2) and cellular protease TMPRSS2 receptors to penetrate the host through the ACE-2 pathway [46]. ACE-2 is a zinc metalloenzyme and transmembrane receptor expressed in the glandular cells of gastric, duodenal and rectal epithelium; pneumocytes of the lungs; enterocytes of the small intestine, heart, kidney, liver and testis; and vascular endothelium cells. ACE-2 serves as an entry point into cells for HCoV-NL63, SARS-CoV and SARS-CoV-2. It coincidentally acts as a receptor for severe acute respiratory syndrome. The density of ACE-2 in each tissue correlates with severity of disease [45,47].