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Abstract Mammals have presumably evolved to adapt to a diverse range of ambient environmental conditions through the optimized heat and mass exchange. One of the crucial biological structures for survivability is the nose, which efficiently transports and thermally preconditions the external air before reaching the internal body. Nasal mucosa and cavity help warm and humidify the inhaled air quickly. Despite its crucial role, the morphological features of mammal noses and their effect in modulating the momentum of the inhaled air, heat transfer dynamics, and particulate trapping remain poorly understood. Tortuosity of the nasal cavity in high-olfactory mammalian species, such as pigs and opossum, facilitates the formation of complex airflow patterns inside the nasal cavity, which leads to the screening of particulates from the inhaled air. We explored basic nasal features in anatomically realistic nasal pathways, including tortuosity, radius of curvature, and gap thickness; they show strong power-law correlations with body weight. Complementary inspection of tortuosity with idealized conduits reveals that this quantity is central in particle capture efficiency. Mechanistic insights into such nuances can serve as a tipping point to transforming nature-based designs into practical applications. In-depth characterization of the fluid–particle interactions in nasal cavities is necessary to uncover nose mechanistic functionalities. It is instrumental in developing new devices and filters in a number of engineering processes. 

The nasopharynx, at the back of the nose, constitutes the dominant initial viral infection trigger zone along the upper respiratory tract. However, as per the standard recommended usage protocol (“Current Use”, or CU) for intranasal sprays, the nozzle should enter the nose almost vertically, resulting in sub-optimal nasopharyngeal drug deposition. Through the Large Eddy Simulation technique, this study has replicated airflow under standard breathing conditions with 15 and 30 L/min inhalation rates, passing through medical scan-based anatomically accurate human airway cavities. The small-scale airflow fluctuations were resolved through use of a sub-grid scale Kinetic Energy Transport Model. Intranasally sprayed droplet trajectories for different spray axis placement and orientation conditions were subsequently tracked via Lagrangian-based inert discrete phase simulations against the ambient inhaled airflow field. Finally, this study verified the computational projections for the upper airway drug deposition trends against representative physical experiments on sprayed delivery performed in a 3D-printed anatomic replica. The model-based exercise has revealed a new “Improved Use” (or, IU) spray usage protocol for viral infections. It entails pointing the spray bottle at a shallower angle (with an almost horizontal placement at the nostril), aiming slightly toward the cheeks. From the conically injected spray droplet simulations, we have summarily derived the following inferences: (a) droplets sized between 7–17  μ m are relatively more efficient at directly reaching the nasopharynx via inhaled transport; and (b) with realistic droplet size distributions, as found in current over-the-counter spray products, the targeted drug delivery through the IU protocol outperforms CU by a remarkable 2 orders-of-magnitude.